While products with calorie-free artificial sugar claim to be as sweet as actual sugar, researchers have claimed that our brains can distinguish real from fake.
Saccharin, the first of the industrially manufactured artificial sweeteners, was discovered late in the 19th century and soon became popular.
Since then, a parade of sweeteners has come on stream, including cyclamate, aspartame, the sucrose-like (and very sweet) sucralose, and several others, including one called Rebiana, derived from a South American herb.
A handful of studies, starting in the 1980s, suggested that regular use of artificial sweeteners might even make people eat more, rather than less, by stimulating their appetites without satisfying them.
And recently, Guido Frank, a psychiatrist at the University of Colorado in Denver who has a particular interest in eating disorders, compared how the brain responds to sucralose and sucrose.
Thus, he fed the sweetener and the sugar to 12 women, adjusting the concentrations so that the sweetness of the two matched.
"They consciously could not distinguish them," New Scientist quoted Frank as saying.
But, when he looked at their brain responses with functional magnetic resonance imaging (fMRI), he saw clear differences.
Sucrose produced stronger activation in the "reward" areas of the brain that light up in response to pleasurable activities such as eating and drinking.
Sucralose didn't activate these areas as strongly, but it synchronised the activity in a whole constellation of taste-associated brain areas - and it did this more strongly than sucrose did.
Frank suggested that sucralose activates brain areas that register pleasant taste, but not strongly enough to cause satiation.
"That might drive you to eat something sweet or something calorific later on," he said.
Similar results emerged from brain-scanning experiments by Paul Smeets, a neuroscientist at Utrecht University Medical Center in the Netherlands, in which he fed volunteers two versions of an orangeade drink.
All these results suggest the brain has some way of detecting calories while food is still in the mouth.
Monday, December 28, 2009
ANTIOXIDENTS RICH FRUITS-Guava
Guava is a fruit that is available in winters. It not only tastes good, but it also has a number of health benefits, too. Nutritionist Ishi Khosla lists some of them: Guava is a rich source of Vitamin C. Thus, it is a good immunity booster. It has high antioxidant properties and it acts as a natural detoxifier. It's a myth that eating guava in winters triggers cold. If eaten in raw form, it provides relief from stomach ailments and gastric troubles.
It is healthy for people who have diabetes and also helps in lowering cholesterol levels.
It is healthy for people who have diabetes and also helps in lowering cholesterol levels.
Wild mushroom extract could treat cancer
An extract from a rare wild mushroom has shown promise in cancer treatment, says a new study.
Cornelia de Moor of University of Nottingham and her team have examined a drug called cordycepin, extracted from a rare kind of wild mushroom called cordyceps and is now prepared from a cultivated form.
'Our discovery will open up the possibility of investigating the range of different cancers that could be treated with cordycepin,' said de Moor.
'We have also developed a very effective method that can be used to test new, more efficient or more stable versions of the drug in the Petri dish,' added de Moor.
Cordyceps is a strange parasitic mushroom that grows on caterpillars. Properties attributed to cordyceps mushroom in Chinese medicine made it interesting to investigate.
The problem was that although cordycepin was a promising drug, it was quickly degraded in the body. It can now be given with another drug to help combat this, but the side effects of the second drug are a limit to its potential use.
'Because of technical obstacles and people moving on to other subjects, it's taken a long time to figure out exactly how cordycepin works on cells,' said de Moor, according to a Nottingham release.
Cornelia de Moor of University of Nottingham and her team have examined a drug called cordycepin, extracted from a rare kind of wild mushroom called cordyceps and is now prepared from a cultivated form.
'Our discovery will open up the possibility of investigating the range of different cancers that could be treated with cordycepin,' said de Moor.
'We have also developed a very effective method that can be used to test new, more efficient or more stable versions of the drug in the Petri dish,' added de Moor.
Cordyceps is a strange parasitic mushroom that grows on caterpillars. Properties attributed to cordyceps mushroom in Chinese medicine made it interesting to investigate.
The problem was that although cordycepin was a promising drug, it was quickly degraded in the body. It can now be given with another drug to help combat this, but the side effects of the second drug are a limit to its potential use.
'Because of technical obstacles and people moving on to other subjects, it's taken a long time to figure out exactly how cordycepin works on cells,' said de Moor, according to a Nottingham release.
Bonding between mother, baby reduces childhood neglect
Strengthening the bond between mother and baby is one way of reducing childhood neglect, says a new study.
University of Queensland (UQ) researcher Lane Strathearn's study identifies how increased pressures placed on mothers by society have reduced the perceived importance of raising children.
'I feel that the basic needs of children have fallen lower and lower on the priority list of families and society, with physical or emotional neglect often the unfortunate result,' Strathearn warned.
'This study emphasises the need to address the basic, universal needs of children, and stresses the importance of this early mother-infant relationship.
'Strengthening this crucial relationship may help to prevent some of the long term consequences of neglect that we are seeing more commonly today, such as delinquency, crime, developmental delay and psychiatric disorders.'
'Our subsequent study showed that the hormone, oxytocin, which is involved in breastfeeding, is also related to secure attachment in mothers and to brain 'reward' activation when they view pictures of their baby,' Strathearn said.
A father of seven, Strathearn grew up in Redcliffe, studied medicine at UQ and completed paediatric training at the Brisbane Mater Children's Hospital, before heading to the US in 2001.
Spanning nine years and drawing upon large longitudinal studies based in Brisbane and brain imaging data collected in Houston, Strathearn's research aimed to develop a better understanding of the pervasive problem of child neglect.
Watching mothers and babies 'connect' was one of the most enjoyable parts of the research, Strathearn said, according to a university release
University of Queensland (UQ) researcher Lane Strathearn's study identifies how increased pressures placed on mothers by society have reduced the perceived importance of raising children.
'I feel that the basic needs of children have fallen lower and lower on the priority list of families and society, with physical or emotional neglect often the unfortunate result,' Strathearn warned.
'This study emphasises the need to address the basic, universal needs of children, and stresses the importance of this early mother-infant relationship.
'Strengthening this crucial relationship may help to prevent some of the long term consequences of neglect that we are seeing more commonly today, such as delinquency, crime, developmental delay and psychiatric disorders.'
'Our subsequent study showed that the hormone, oxytocin, which is involved in breastfeeding, is also related to secure attachment in mothers and to brain 'reward' activation when they view pictures of their baby,' Strathearn said.
A father of seven, Strathearn grew up in Redcliffe, studied medicine at UQ and completed paediatric training at the Brisbane Mater Children's Hospital, before heading to the US in 2001.
Spanning nine years and drawing upon large longitudinal studies based in Brisbane and brain imaging data collected in Houston, Strathearn's research aimed to develop a better understanding of the pervasive problem of child neglect.
Watching mothers and babies 'connect' was one of the most enjoyable parts of the research, Strathearn said, according to a university release
Saturday, December 26, 2009
New discovery may help develop drugs that kill cancer cells
Scientists claim to have identified a family of "limpet-like" proteins that appears to play a vital role in repairing DNA damage which triggers cancer.
They hope that the finding may lead to new drugs, which could help kill cancer cells, and promote production of healthy replacements.
The Small Ubiquitin-like Modifier (SUMO) proteins appear to have a remarkable ability to zero in on the damaged areas.
They bind to normal proteins and direct them in to repair genetic glitches.
With this method, the proteins were even able to repair double strand DNA breaks - the most severe type of DNA damage.
And after the work is complete, the proteins detach themselves and move on.
The researchers focussed their study on BRCA1 gene, which, if damaged, is associated with a very high risk of breast cancer.
SUMO was shown to attach to the damaged gene, and switch it back on - helping prevent breast cancer forming.
"This new insight is the first step towards developing drugs which may protect normal cells from the side effects of chemotherapy, or improve the effectiveness of current breast cancer treatments," BBC News quoted Researcher Dr Jo Morris, from King's College London, as saying.
"DNA damage, particularly double strand DNA breaks, are a fundamental cause of cancer and we know that people who have mutations in the BRCA1 gene have a higher risk of developing some kinds of cancer," said Dr Lesley Walker, of Cancer Research UK, which part-funded the study
"Discovering that these limpet-like proteins play such an important role in repair may provide new opportunities to stop cancer from growing.
"This is an extremely complex and intricate biological process so it may be many years before we can use this knowledge to safely intervene and help treat cancer patients
They hope that the finding may lead to new drugs, which could help kill cancer cells, and promote production of healthy replacements.
The Small Ubiquitin-like Modifier (SUMO) proteins appear to have a remarkable ability to zero in on the damaged areas.
They bind to normal proteins and direct them in to repair genetic glitches.
With this method, the proteins were even able to repair double strand DNA breaks - the most severe type of DNA damage.
And after the work is complete, the proteins detach themselves and move on.
The researchers focussed their study on BRCA1 gene, which, if damaged, is associated with a very high risk of breast cancer.
SUMO was shown to attach to the damaged gene, and switch it back on - helping prevent breast cancer forming.
"This new insight is the first step towards developing drugs which may protect normal cells from the side effects of chemotherapy, or improve the effectiveness of current breast cancer treatments," BBC News quoted Researcher Dr Jo Morris, from King's College London, as saying.
"DNA damage, particularly double strand DNA breaks, are a fundamental cause of cancer and we know that people who have mutations in the BRCA1 gene have a higher risk of developing some kinds of cancer," said Dr Lesley Walker, of Cancer Research UK, which part-funded the study
"Discovering that these limpet-like proteins play such an important role in repair may provide new opportunities to stop cancer from growing.
"This is an extremely complex and intricate biological process so it may be many years before we can use this knowledge to safely intervene and help treat cancer patients
Why aging prevents sleep from enhancing memory
Numerous studies have shown that sleep helps boost memory. However, aging prevents the brain from reaping that benefit. Now, scientists are trying to decode why does that happen.
Psychologist Rebecca Spencer, who is the director of the Cognition and Action Lab in the UMass Amherst department of psychology, says one explanation could be that as people age, they sleep less and some critical stages of sleep are interrupted more frequently.
This suggests that it is not a change in the overall quantity of sleep that reduces the benefits sleep conveys on memory, but rather to the quality of specific sleep stages that makes the difference.
Spencer said that motor learning, the processes underlying learning to play tennis, golf or the piano, is boosted during stage two of non-REM sleep (nREM-2).
While older adults often sleep less than when they were young, nREM-2 is preserved and may even increase.
The downside, however, is that this stage of sleep is interrupted more in older people. Older adults are defined in the study as being 54 to 80 years old.
"When you sleep, the brain replays the 'movie' from your day and we believe this is how sleep improves memory. As we grow old, that movie might play a bit longer, but it is also interrupted more frequently," Spencer said.
She said that current research points to the need for continuity in nREM-2 sleep to generate the sleep benefit.
Psychologist Rebecca Spencer, who is the director of the Cognition and Action Lab in the UMass Amherst department of psychology, says one explanation could be that as people age, they sleep less and some critical stages of sleep are interrupted more frequently.
This suggests that it is not a change in the overall quantity of sleep that reduces the benefits sleep conveys on memory, but rather to the quality of specific sleep stages that makes the difference.
Spencer said that motor learning, the processes underlying learning to play tennis, golf or the piano, is boosted during stage two of non-REM sleep (nREM-2).
While older adults often sleep less than when they were young, nREM-2 is preserved and may even increase.
The downside, however, is that this stage of sleep is interrupted more in older people. Older adults are defined in the study as being 54 to 80 years old.
"When you sleep, the brain replays the 'movie' from your day and we believe this is how sleep improves memory. As we grow old, that movie might play a bit longer, but it is also interrupted more frequently," Spencer said.
She said that current research points to the need for continuity in nREM-2 sleep to generate the sleep benefit.
Daily sex 'helps improve sperm quality'
Having sex every day improves men's sperm quality, an Australian study has revealed.
In a study of men with fertility problems, researchers found that daily ejaculation for a week cut the amount of DNA damage seen in sperm samples.
"All that we knew was that intercourse on the day of ovulation offered the highest chance of pregnancy, but we did not know what was the best advice for the period leading up to ovulation or egg retrieval for IVF," Dr David Greening, an obstetrician and gynaecologist with sub specialist training in reproductive endocrinology and infertility at Sydney IVF, Wollongong, Australia, said.
"I thought that frequent ejaculation might be a physiological mechanism to improve sperm DNA damage, while maintaining semen levels within the normal, fertile range," he added.
To investigate this hypothesis, Greening studied 118 men who had higher than normal sperm DNA damage as indicated by a DNA Fragmentation Index (DFI).
Men who had a more than 15 percent of their sperm damaged were eligible for the trial. At Sydney IVF, sperm DNA damage is defined as less than 15 percent DFI for excellent quality sperm, 15-24 percent DFI for good, 25-29 percent DFI for fair and more than 29 percent DFI for poor quality; but other laboratories can have slightly different ranges.
The men were instructed to ejaculate daily for seven days, and no other treatment or lifestyle changes were suggested. Before they started, levels of DNA damage ranged between 15 percent and 98 percent DFI, with an average 34 percent DFI when measured after three days' abstinence.
When the men's sperm was re-assessed on the seventh day, Greening found that 81 percent men had an average 12 percent decrease in their sperm DNA damage, while 19 percent men and an average increase in damage of nearly 10 percent. The average for the whole group dropped to 26 percent DFI.
"Although the mean average was 26 percent which is in the 'fair' range for sperm quality, this included 18 percent of men whose sperm DNA damage increased as well as those whose DNA damage decreased," Greening said.
"Amongst the men whose damage decreased, their average dropped by 12 percent to just under 23 percent DFI, which puts them in the 'good' range. Also, more men moved into the 'good' range and out of the 'poor' or 'fair' range. These changes were substantial and statistically highly significant.
"In addition, we found that although frequent ejaculation decreased semen volume and sperm concentrations, it did not compromise sperm motility and, in fact, this rose slightly but significantly.
"Further research is required to see whether the improvement in these men's sperm quality translates into better pregnancy rates, but other, previous studies have shown the relationship between sperm DNA damage and pregnancy rates," he added.
Greening said he thought the reason why sperm quality improved with frequent ejaculation was because the sperm had a shorter exposure in the testicular ducts and epididymis to reactive oxygen species - very small molecules, high levels of which can damage cells.
"The remainder of the men who had an increase in DFI might have a different explanation for their sperm DNA damage," he said.
The study has been presented at the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam.
In a study of men with fertility problems, researchers found that daily ejaculation for a week cut the amount of DNA damage seen in sperm samples.
"All that we knew was that intercourse on the day of ovulation offered the highest chance of pregnancy, but we did not know what was the best advice for the period leading up to ovulation or egg retrieval for IVF," Dr David Greening, an obstetrician and gynaecologist with sub specialist training in reproductive endocrinology and infertility at Sydney IVF, Wollongong, Australia, said.
"I thought that frequent ejaculation might be a physiological mechanism to improve sperm DNA damage, while maintaining semen levels within the normal, fertile range," he added.
To investigate this hypothesis, Greening studied 118 men who had higher than normal sperm DNA damage as indicated by a DNA Fragmentation Index (DFI).
Men who had a more than 15 percent of their sperm damaged were eligible for the trial. At Sydney IVF, sperm DNA damage is defined as less than 15 percent DFI for excellent quality sperm, 15-24 percent DFI for good, 25-29 percent DFI for fair and more than 29 percent DFI for poor quality; but other laboratories can have slightly different ranges.
The men were instructed to ejaculate daily for seven days, and no other treatment or lifestyle changes were suggested. Before they started, levels of DNA damage ranged between 15 percent and 98 percent DFI, with an average 34 percent DFI when measured after three days' abstinence.
When the men's sperm was re-assessed on the seventh day, Greening found that 81 percent men had an average 12 percent decrease in their sperm DNA damage, while 19 percent men and an average increase in damage of nearly 10 percent. The average for the whole group dropped to 26 percent DFI.
"Although the mean average was 26 percent which is in the 'fair' range for sperm quality, this included 18 percent of men whose sperm DNA damage increased as well as those whose DNA damage decreased," Greening said.
"Amongst the men whose damage decreased, their average dropped by 12 percent to just under 23 percent DFI, which puts them in the 'good' range. Also, more men moved into the 'good' range and out of the 'poor' or 'fair' range. These changes were substantial and statistically highly significant.
"In addition, we found that although frequent ejaculation decreased semen volume and sperm concentrations, it did not compromise sperm motility and, in fact, this rose slightly but significantly.
"Further research is required to see whether the improvement in these men's sperm quality translates into better pregnancy rates, but other, previous studies have shown the relationship between sperm DNA damage and pregnancy rates," he added.
Greening said he thought the reason why sperm quality improved with frequent ejaculation was because the sperm had a shorter exposure in the testicular ducts and epididymis to reactive oxygen species - very small molecules, high levels of which can damage cells.
"The remainder of the men who had an increase in DFI might have a different explanation for their sperm DNA damage," he said.
The study has been presented at the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam.
Friday, December 25, 2009
1.1DETERMNATIN OF AOA BY ANTIRADICAL ACTIVITY (DPPH):
Principle:
Determination of scavenging activity of the 1,1-diphenyl-2-picylhydrazyl (DPPH) free radical is a very fast method to evaluate the anti oxidant activity of the extract. When DPPH radical is scavenged by the anti oxidant activity through donation of hydrogen to form stable DPPH-H molecule, color changes from purple to yellow and this is monitored by measuring the decrease in optical absorbance at 517 nm.
Reagents:
DPPH reagent (1,1-diphenyl-2-picylhydrazyl)
Ascorbic acid (standard)
Methanol (100%)
Distilled water
Method:
DPPH*(2,2’-diphenyl-1-picrylhydrazyl) scavenging activity was determined using a modified method of Brand-Williams et al., 0.1 mM DPPH* was dissolved in 80% aqueous methanol 0.1 ml of the extracted sample was taken and 2.9 ml of the methanolic DPPH* solution was added and kept in the dark for 30 min and read at 517 nm. The standard sample is taken as µg equivalent ascorbic acid present in one gram of food sample. A standard graph was run with ascorbic acid and AOA of the samples, quantity of ascorbic acid and the optical absorbance at 517 nms. The total AOA of the foods are expressed in this thesis as mg ascorbic acid equivalent in 1 gm of the edible portion of that food stuff.
Determination of scavenging activity of the 1,1-diphenyl-2-picylhydrazyl (DPPH) free radical is a very fast method to evaluate the anti oxidant activity of the extract. When DPPH radical is scavenged by the anti oxidant activity through donation of hydrogen to form stable DPPH-H molecule, color changes from purple to yellow and this is monitored by measuring the decrease in optical absorbance at 517 nm.
Reagents:
DPPH reagent (1,1-diphenyl-2-picylhydrazyl)
Ascorbic acid (standard)
Methanol (100%)
Distilled water
Method:
DPPH*(2,2’-diphenyl-1-picrylhydrazyl) scavenging activity was determined using a modified method of Brand-Williams et al., 0.1 mM DPPH* was dissolved in 80% aqueous methanol 0.1 ml of the extracted sample was taken and 2.9 ml of the methanolic DPPH* solution was added and kept in the dark for 30 min and read at 517 nm. The standard sample is taken as µg equivalent ascorbic acid present in one gram of food sample. A standard graph was run with ascorbic acid and AOA of the samples, quantity of ascorbic acid and the optical absorbance at 517 nms. The total AOA of the foods are expressed in this thesis as mg ascorbic acid equivalent in 1 gm of the edible portion of that food stuff.
EXTRACTION OF ANTIOXIDANTS
Scientists complete sequencing Tibetan antelope genome
Chinese scientists said Friday they have completed sequencing the genome of the Tibetan antelope which will hopefully explain the pathogenesis of chronic plateau sickness.
Tibetan antelopes, which live on China's Qinghai-Tibet Plateau, have been given the highest level of protection under the UN Convention on International Trade in Endangered Species since 1979, and listed among the most endangered species by the Chinese government since 1988.
They are considered to be ideal species for evolution studies, as they had lived on 'the Roof of the World' for millions of years against the backdrop of various environmental extremes, such as extreme cold and low oxygen levels.
'By sequencing the Tibetan antelope genome, we have laid the scientific foundation to decode the pathogenesis of chronic plateau sickness,' said Yang Huanming, an academician of the Chinese Academy of Sciences and a participant of the project.
'The studies can also contribute to improving the health of the plateau inhabitants, especially those of Tibetan ethnic group that has lived on the plateau generations after generations,' he said.
The project was jointly launched by the Qinghai University and the Beijing Genomics Institute's Shenzhen branch in April this year.
In addition to Tibetan antelopes, scientists are working to sequence the genomes of penguins and polar bears as part of the project.
'Sequencing the Tibetan antelope genome also lays the genetic foundation for us to carry out plateau life sciences studies, but it is only the first step,' said Gerili, vice president of the Qinghai University and director of the International Society for Mountain Medicine.
'We will further identify the functors on the genome, decode all the genetic information, and explore the genetic basis of Tibetan antelopes' ability to evolve and to adapt to harsh environment,' he said.
It is the world's first genome sequencing project for endangered species which live on the plateaus, he added.
Chinese scientists have contributed to the genome sequencing of rice, silkworm, hen, pig and giant panda. In October 2007, they finished sequencing the first Han Chinese genome.
Wednesday, December 23, 2009
METAL MEDIATED FREE RADICAL GENERATION
Metal-mediated formation of free radicals causes various modifications to DNA bases, enhanced lipid per oxidation, and altered calcium and sulfhydryl homeostasis. Lipid peroxides, formed by the attack of radicals on polyunsaturated fatty acid residues of phospholipids, can further react with redox metals finally producing mutagenic and carcinogenic malondialdehyde, 4-hydroxynonenal and other exocyclic DNA adducts (etheno and/or propano adducts). The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. Common mechanisms involving the Fenton reaction, generation of the superoxide radical and the hydroxyl radical appear to be involved for iron, copper, chromium, vanadium and cobalt primarily associated with mitochondria, microsomes and peroxisomes. . Nitric oxide (NO) seems to be involved in arsenite-induced DNA damage and pyrimidine excision inhibition.
OXIDATIVE STRESS IN HEALTH AND DISEASE
In Cells, oxidation process uses oxygen to produce energy for biochemical reactions. During these reactions, the free radicals/Reactive oxygen species(ROS) are produced as byproducts of metabolic process.The overproduction of free radicals and reactive oxygen species (ROS) is a common underlying mechanism of many neuropathology’s, as they have been shown to damage various cellular components, including proteins, lipids and DNA. Oxidative stress occurs when the production of these potentially destructive reactive oxygen species (ROS) exceeds the bodies own natural antioxidant defenses, resulting in cellular damage. The higher and frequent consumption of protective food like fruit, vegetables, vegetable oils, nuts, seeds and cereal grains is recommended in prevention of free radical disease.
2.1.1OXIDATIVE STRESS:
Oxidative stress is a state characterized by an excess of reactive oxygen species (ROS) in the body, which creates a potentially unstable cellular environment that is associated with tissue damage accelerated aging and degenerative diseases. Free radicals and reactive oxygen species (ROS) are species with incomplete electron shells that make them move chemically reactive than those with complete electron shells. They are byproducts of metabolic processes. Some of the reactive species which are of particular interest from the point of view of oxidative stress are
· Super oxide radical (O(2)(-)),
· hydroxyl radical (HO()),
· peroxyl radical (ROO())
· Hydrogen peroxide (H(2)O(2))
· Alkoxyl radical
· singlet oxygen ((1)O(2))
· nitric oxide (()NO)
· peroxynitrite (ONOO(-))
Oxidative stress is induced by a wide range of environmental factors including UV stress, pathogen invasion (hypersensitive reaction), herbicide action, oxygen shortage, cigarette smoke, automobile exhaust fumes, air pollutants.There are numerous types of free radicals that can be formed within the body. The most common ROS include: the superoxide anion (O2-), the hydroxyl radical (OH ·), singlet oxygen (One O2), and hydrogen peroxide (H2O2). Superoxide anions are formed when oxygen (O2) acquires an additional electron, leaving the molecule with only one unpaired electron. Within the mitochondria O2- · is continuously being formed. The rate of formation depends on the amount of oxygen flowing through the mitochondria at any given time. Hydroxyl radicals are short-lived, but are the most damaging radicals within the body. This type of free radical can be formed from O2- and H2O2 via the Harber-Weiss reaction. The interaction of copper or iron and H2O2 also produce OH · as first observed by Fenton. These reactions are significant as the substrates are found within the body and could easily interact.Hydrogen peroxide is produced in vivo by many reactions. Hydrogen peroxide is unique in that it can be converted to the highly damaging hydroxyl radical or be catalyzed and excreted harmlessly as water. Glutathione peroxidase is essential for the conversion of glutathione to oxidized glutathione, during which H2O2 is converted to water.If H2O2 is not converted into water, instead singlet oxygen (one O2) is formed. Singlet oxygen is not a free radical, but can be formed during radical reactions and also cause further reactions. Singlet oxygen violates Hund's rule of electron filling in that it has eight outer electrons existing in pairs leaving one orbital of the same energy level empty. When oxygen is energetically excited one of the electrons can jump to empty orbital creating unpaired electrons. Singlet oxygen can then transfer the energy to a new molecule and act as a catalyst for free radical formation. The molecule can also interact with other molecules leading to the formation of a new free radical.
2.1.2PRODUCTION OF FREE RADICALS IN THE HUMAN BODY:
Free radicals and other reactive oxygen species are derived either from normal essential metabolic processes in the human body or from external sources such as exposure to X-rays, ozone, cigarette smoking, air pollutants and industrial chemicals.
Free radical formation occurs continuously in the cells as a consequence of both enzymatic and non-enzymatic reactions. Enzymatic reactions which serve as sources of free radicals include those involved in the respiratory chain, in phagocytosis, in prostaglandin synthesis and in the cytochrome P450 system. Free radicals also arise in non-enzymatic reactions of oxygen with organic compounds as well as those initiated by ionizing radiations.
Some internally generated sources of free radicals are:
Mitochondria
Phagocytes
Xanthine oxidase
Reactions involving iron and other transition metals
Arachidonate pathways
Peroxisomes
Exercise
Inflammation
Ischaemia/reperfusion.
Some externally generated sources of free radicals are:
Cigarette smoke
Environmental pollutants
Radiation
Ultraviolet light
Certain drugs, pesticides, anesthetics and industrial solvents
Ozone.
If free radicals are not inactivated, their chemical reactivity can damage all cellular macromolecules including proteins, carbohydrates, lipids and nucleic acids. Their destructive effects on proteins may play a role in the causation of cataracts. Free radical damage to DNA is also implicated in the causation of cancer and its effect on LDL cholesterol is very likely responsible for heart disease. In fact, the theory associating free radicals with the aging process has also gained widespread acceptance.
2.1.3 IMPORTANCE OF FREE RADICALS:
Free radicals are naturally produced taken within the body and have beneficial effects that cannot be overlooked. The immune system is the main body system that utilizes free radicals. Foreign invaders or damaged tissue is marked with free radicals by the immune system. This allows for determination of which tissue need to be removed from the body. Because of this there is a need for antioxidant supplementation.
2.1.4OXIDATIVE STRESS IN VARIOUS PHYSIOLOGICAL STAGES: Oxidative stress occurs during various physiological conditions like in infants and during ageing. Infants: Respiratory distress syndrome (RDS) incidence is increased in infants of pre-clamptic mothers with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. RDS and HELLP syndrome have been associated with oxidative stress and inflammatory processes. Oxidative stress is a risk factor for broncho -pulmonary dysplasia in the preterm Newborn. Antioxidant defense is impaired in the preterm newborn. Oxidative stress is also involved in cell growth and development. It is shown that oxygen-derived free radicals, and particularly the super oxide anion, are intermediaries in the formation and activation of osteoclasts. Many antioxidant defense systems depend on micronutrients or are micronutrients themselves. Oxidative stress related to bone indices in newborn infants. Aging:It was proposed that free radicals are the major factor involved in aging process. This gave birth to the free radical theory of aging. This current theory provides the most popular explanation for how aging occurs at the biochemical/molecular level. Ever since1956, this theory has received widespread attention and a large body of evidence has been accumulated in support of its hypotheses which were subsequently refined. The free radical theory of aging postulates that age-associated reductions in physiological functions are caused by an irreversible accumulation of oxidative alterations to macromolecules. This accumulation increases with age and is associated with the life expectancy of organisms. Moreover, this theory suggests the existence of an imbalance between reactive oxygen species (ROS)-producing pathways and (ROS)-scavenging pathways, which is responsible for the generation of oxidative stress syndrome. The free radical theory of aging hypothesizes that oxygen-derived free radicals are responsible for the age-related damage at the cellular and tissue levels. In a normal situation, a balanced-equilibrium exists among oxidants, antioxidants and biomolecules. Excess generation of free radicals may overwhelm natural cellular antioxidant defenses leading to oxidation and further contributing to cellular functional impairment. The identification of free radical reactions as promoters of the aging process implies that interventions aimed at limiting or inhibiting them should be able to reduce the rate of formation of aging changes with a consequent reduction of the aging rate and disease pathogenesis. 2.1.5OXIDATIVE STRESS IN VARIOUS DISEASES:
A growing body of evidence suggests oxidative stress involvement in neurodegenerative diseases; however, it remains to be determined whether oxidative stress is a cause, result, or epiphenomenon of the pathological processes.ROS contribute to oxidative stress ,which is linked to numerous degenerative conditions including cardiovascular disease, inflammation,, Alzheimer’s disease Parkinson’s disease, diabetes and Aging etc. Few other conditions associated with oxidative stress are presented in table 1.
1. Conditions associated with oxidative damage:
• Atherosclerosis
• Cancer
• Pulmonary dysfunction
• Cataracts
•Arthritis and inflammatory diseases
• Diabetes
•Shock, trauma and ischemia
• Renal disease and hemodialysis
Mechanisms involved in the role of ROS and oxidative stress in disease development may include alteration of important biomolecules causing oxidative modifications in nucleic acids, modulation of gene expression through activation of redox sensitive transcription factors and modulation of inflammatory responses through signal transduction.
2.1.6EFFECT OF OXIDATIVE STRESS ON BIOLOGICAL MICRO MOLECULES: ROS are highly reactive and their accumulation induces cell damage by modifying molecules, including lipids, proteins and DNA. Oxidative DNA damage in humans could arise also from incorrect nutritional habit and life style. DNA strand breaks with apurinic/apyrimidinic sites, oxidized purines and oxidized pyrimidines.The main cellular components susceptible to damage by free radicals are lipids (per-oxidation of unsaturated fatty acids in membranes), proteins (denaturation), carbohydrates and nucleic acids. Hypoxia also induces oxidative stress which depend on tissue and/or species (i.e. their tolerance to anoxia), on membrane properties, on endogenous antioxidant content and on the ability to induce the response in the antioxidant system. Radicals react with lipids and cause oxidative destruction of unsaturated that is; Polyunsaturated fatty acids, known as lipid per oxidation. Both lipids in biological systems and lipids as food constituents are submitted to this process. Lipid per oxidation in cells leads to direct damage of cell membranes with indirect damages of other cell constituents, caused by reactivity of secondary products of this reaction, aldehydes. This complex reaction is responsible for damages of many tissues and progress of some diseases (atherosclerosis).
2.1.7METAL MEDIATED FREE RADICAL GENERATION:
Metal-mediated formation of free radicals causes various modifications to DNA bases, enhanced lipid per oxidation, and altered calcium and sulfhydryl homeostasis. Lipid peroxides, formed by the attack of radicals on polyunsaturated fatty acid residues of phospholipids, can further react with redox metals finally producing mutagenic and carcinogenic malondialdehyde, 4-hydroxynonenal and other exocyclic DNA adducts (etheno and/or propano adducts). The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. Common mechanisms involving the Fenton reaction, generation of the superoxide radical and the hydroxyl radical appear to be involved for iron, copper, chromium, vanadium and cobalt primarily associated with mitochondria, microsomes and peroxisomes. . Nitric oxide (NO) seems to be involved in arsenite-induced DNA damage and pyrimidine excision inhibition.
2.1.1OXIDATIVE STRESS:
Oxidative stress is a state characterized by an excess of reactive oxygen species (ROS) in the body, which creates a potentially unstable cellular environment that is associated with tissue damage accelerated aging and degenerative diseases. Free radicals and reactive oxygen species (ROS) are species with incomplete electron shells that make them move chemically reactive than those with complete electron shells. They are byproducts of metabolic processes. Some of the reactive species which are of particular interest from the point of view of oxidative stress are
· Super oxide radical (O(2)(-)),
· hydroxyl radical (HO()),
· peroxyl radical (ROO())
· Hydrogen peroxide (H(2)O(2))
· Alkoxyl radical
· singlet oxygen ((1)O(2))
· nitric oxide (()NO)
· peroxynitrite (ONOO(-))
Oxidative stress is induced by a wide range of environmental factors including UV stress, pathogen invasion (hypersensitive reaction), herbicide action, oxygen shortage, cigarette smoke, automobile exhaust fumes, air pollutants.There are numerous types of free radicals that can be formed within the body. The most common ROS include: the superoxide anion (O2-), the hydroxyl radical (OH ·), singlet oxygen (One O2), and hydrogen peroxide (H2O2). Superoxide anions are formed when oxygen (O2) acquires an additional electron, leaving the molecule with only one unpaired electron. Within the mitochondria O2- · is continuously being formed. The rate of formation depends on the amount of oxygen flowing through the mitochondria at any given time. Hydroxyl radicals are short-lived, but are the most damaging radicals within the body. This type of free radical can be formed from O2- and H2O2 via the Harber-Weiss reaction. The interaction of copper or iron and H2O2 also produce OH · as first observed by Fenton. These reactions are significant as the substrates are found within the body and could easily interact.Hydrogen peroxide is produced in vivo by many reactions. Hydrogen peroxide is unique in that it can be converted to the highly damaging hydroxyl radical or be catalyzed and excreted harmlessly as water. Glutathione peroxidase is essential for the conversion of glutathione to oxidized glutathione, during which H2O2 is converted to water.If H2O2 is not converted into water, instead singlet oxygen (one O2) is formed. Singlet oxygen is not a free radical, but can be formed during radical reactions and also cause further reactions. Singlet oxygen violates Hund's rule of electron filling in that it has eight outer electrons existing in pairs leaving one orbital of the same energy level empty. When oxygen is energetically excited one of the electrons can jump to empty orbital creating unpaired electrons. Singlet oxygen can then transfer the energy to a new molecule and act as a catalyst for free radical formation. The molecule can also interact with other molecules leading to the formation of a new free radical.
2.1.2PRODUCTION OF FREE RADICALS IN THE HUMAN BODY:
Free radicals and other reactive oxygen species are derived either from normal essential metabolic processes in the human body or from external sources such as exposure to X-rays, ozone, cigarette smoking, air pollutants and industrial chemicals.
Free radical formation occurs continuously in the cells as a consequence of both enzymatic and non-enzymatic reactions. Enzymatic reactions which serve as sources of free radicals include those involved in the respiratory chain, in phagocytosis, in prostaglandin synthesis and in the cytochrome P450 system. Free radicals also arise in non-enzymatic reactions of oxygen with organic compounds as well as those initiated by ionizing radiations.
Some internally generated sources of free radicals are:
Mitochondria
Phagocytes
Xanthine oxidase
Reactions involving iron and other transition metals
Arachidonate pathways
Peroxisomes
Exercise
Inflammation
Ischaemia/reperfusion.
Some externally generated sources of free radicals are:
Cigarette smoke
Environmental pollutants
Radiation
Ultraviolet light
Certain drugs, pesticides, anesthetics and industrial solvents
Ozone.
If free radicals are not inactivated, their chemical reactivity can damage all cellular macromolecules including proteins, carbohydrates, lipids and nucleic acids. Their destructive effects on proteins may play a role in the causation of cataracts. Free radical damage to DNA is also implicated in the causation of cancer and its effect on LDL cholesterol is very likely responsible for heart disease. In fact, the theory associating free radicals with the aging process has also gained widespread acceptance.
2.1.3 IMPORTANCE OF FREE RADICALS:
Free radicals are naturally produced taken within the body and have beneficial effects that cannot be overlooked. The immune system is the main body system that utilizes free radicals. Foreign invaders or damaged tissue is marked with free radicals by the immune system. This allows for determination of which tissue need to be removed from the body. Because of this there is a need for antioxidant supplementation.
2.1.4OXIDATIVE STRESS IN VARIOUS PHYSIOLOGICAL STAGES: Oxidative stress occurs during various physiological conditions like in infants and during ageing. Infants: Respiratory distress syndrome (RDS) incidence is increased in infants of pre-clamptic mothers with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. RDS and HELLP syndrome have been associated with oxidative stress and inflammatory processes. Oxidative stress is a risk factor for broncho -pulmonary dysplasia in the preterm Newborn. Antioxidant defense is impaired in the preterm newborn. Oxidative stress is also involved in cell growth and development. It is shown that oxygen-derived free radicals, and particularly the super oxide anion, are intermediaries in the formation and activation of osteoclasts. Many antioxidant defense systems depend on micronutrients or are micronutrients themselves. Oxidative stress related to bone indices in newborn infants. Aging:It was proposed that free radicals are the major factor involved in aging process. This gave birth to the free radical theory of aging. This current theory provides the most popular explanation for how aging occurs at the biochemical/molecular level. Ever since1956, this theory has received widespread attention and a large body of evidence has been accumulated in support of its hypotheses which were subsequently refined. The free radical theory of aging postulates that age-associated reductions in physiological functions are caused by an irreversible accumulation of oxidative alterations to macromolecules. This accumulation increases with age and is associated with the life expectancy of organisms. Moreover, this theory suggests the existence of an imbalance between reactive oxygen species (ROS)-producing pathways and (ROS)-scavenging pathways, which is responsible for the generation of oxidative stress syndrome. The free radical theory of aging hypothesizes that oxygen-derived free radicals are responsible for the age-related damage at the cellular and tissue levels. In a normal situation, a balanced-equilibrium exists among oxidants, antioxidants and biomolecules. Excess generation of free radicals may overwhelm natural cellular antioxidant defenses leading to oxidation and further contributing to cellular functional impairment. The identification of free radical reactions as promoters of the aging process implies that interventions aimed at limiting or inhibiting them should be able to reduce the rate of formation of aging changes with a consequent reduction of the aging rate and disease pathogenesis. 2.1.5OXIDATIVE STRESS IN VARIOUS DISEASES:
A growing body of evidence suggests oxidative stress involvement in neurodegenerative diseases; however, it remains to be determined whether oxidative stress is a cause, result, or epiphenomenon of the pathological processes.ROS contribute to oxidative stress ,which is linked to numerous degenerative conditions including cardiovascular disease, inflammation,, Alzheimer’s disease Parkinson’s disease, diabetes and Aging etc. Few other conditions associated with oxidative stress are presented in table 1.
1. Conditions associated with oxidative damage:
• Atherosclerosis
• Cancer
• Pulmonary dysfunction
• Cataracts
•Arthritis and inflammatory diseases
• Diabetes
•Shock, trauma and ischemia
• Renal disease and hemodialysis
Mechanisms involved in the role of ROS and oxidative stress in disease development may include alteration of important biomolecules causing oxidative modifications in nucleic acids, modulation of gene expression through activation of redox sensitive transcription factors and modulation of inflammatory responses through signal transduction.
2.1.6EFFECT OF OXIDATIVE STRESS ON BIOLOGICAL MICRO MOLECULES: ROS are highly reactive and their accumulation induces cell damage by modifying molecules, including lipids, proteins and DNA. Oxidative DNA damage in humans could arise also from incorrect nutritional habit and life style. DNA strand breaks with apurinic/apyrimidinic sites, oxidized purines and oxidized pyrimidines.The main cellular components susceptible to damage by free radicals are lipids (per-oxidation of unsaturated fatty acids in membranes), proteins (denaturation), carbohydrates and nucleic acids. Hypoxia also induces oxidative stress which depend on tissue and/or species (i.e. their tolerance to anoxia), on membrane properties, on endogenous antioxidant content and on the ability to induce the response in the antioxidant system. Radicals react with lipids and cause oxidative destruction of unsaturated that is; Polyunsaturated fatty acids, known as lipid per oxidation. Both lipids in biological systems and lipids as food constituents are submitted to this process. Lipid per oxidation in cells leads to direct damage of cell membranes with indirect damages of other cell constituents, caused by reactivity of secondary products of this reaction, aldehydes. This complex reaction is responsible for damages of many tissues and progress of some diseases (atherosclerosis).
2.1.7METAL MEDIATED FREE RADICAL GENERATION:
Metal-mediated formation of free radicals causes various modifications to DNA bases, enhanced lipid per oxidation, and altered calcium and sulfhydryl homeostasis. Lipid peroxides, formed by the attack of radicals on polyunsaturated fatty acid residues of phospholipids, can further react with redox metals finally producing mutagenic and carcinogenic malondialdehyde, 4-hydroxynonenal and other exocyclic DNA adducts (etheno and/or propano adducts). The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. Common mechanisms involving the Fenton reaction, generation of the superoxide radical and the hydroxyl radical appear to be involved for iron, copper, chromium, vanadium and cobalt primarily associated with mitochondria, microsomes and peroxisomes. . Nitric oxide (NO) seems to be involved in arsenite-induced DNA damage and pyrimidine excision inhibition.
Saturday, December 12, 2009
MECHANISM OF ANTIOXIDANTS IN THE BODY
Antioxidants provide protection against oxidative attack by decreasing oxygen concentration, intercepting singlet oxygen, preventing first chain initiation by scavenging initial radicals, binding of metal ion catalysts, decomposing the primary products of oxidation to non radical compounds and chain breaking to prevent continuous hydrogen removal from substrates.
Antioxidants react with radicals and other reactive species faster than biological substrates, thus protecting biological targets from oxidative damage. Further more the resulting anti oxidant radical possess high stability that is the antioxidant radical interrupts (rather than propagate) a chain reaction.
2.4. EXOGENOUS ANTIOXIDANT SYSTEM:
The body gets some of its antioxidants from the environment, more specifically from the food that is consumed (exogenous antioxidants). While the enzymatic antioxidants are intrinsic to the organism, the non-enzymatic components are both of intrinsic and exogenous nature. The non-enzymatic antioxidants consist of nutrient and non nutrient compounds.
2.4.1ENZYMATIC ANTIOXIDANTS:
Among the enzymatic antioxidants mainly three groups of enzymes play significant roles in protecting cells from oxidant stress:
Superoxide Dismutases (SOD) are enzymes that catalyze the conversion of two super oxides into hydrogen peroxide and oxygen. The benefit here is that hydrogen peroxide is substantially less toxic that superoxide. SOD accelerates this detoxifying reaction roughly 10,000-fold over the non-catalyzed reaction.
SODs are metal-containing enzymes that depend on bound manganese, copper or zinc for their antioxidant activity. In mammals, the manganese-containing enzyme is most abundant in mitochondria, while the zinc or copper forms predominant in cytoplasm. Interestingly, SODs are inducible enzymes - exposure of bacteria or vertebrate cells to higher concentrations of oxygen results in rapid increases in the concentration of SOD.
Catalase is found in peroxisomes in eucaryotic cells. It degrades hydrogen peroxide to water and oxygen, and hence finishes the detoxification reaction started by SOD.
Glutathione peroxidase is a group of enzymes, the most abundant of which contain selenium. These enzymes, like catalase, degrade hydrogen peroxide. They also reduce organic peroxides to alcohols, providing another route for eliminating toxic oxidants.In addition to these enzymes, glutathione transferase, ceruloplasmin, hemoxygenase and possibly several other enzymes may participate in enzymatic control of oxygen radicals and their products.
2.4.2NON –ENZYMATIC ANTIOXIDANTS:
NUTRIENT COMPOUNDS:
Vitamin C:
Ascorbate, an essential vitamin found in fruits and vegetables, has been particularly well studied in its role as an antioxidant and is suggested to serve several physiological functions including (1) preventing free-radical-induced damage to DNA, (2) quenching oxidants which can lead to the development of cataracts, (3) improving endothelial cell dysfunction, and (4) decreasing LDL induced leukocyte adhesion. Vitamin C readily scavenges reactive oxygen and nitrogen species and may thereby prevent oxidative damage to important biological macromolecules such as DNA, lipids, and proteins. Vitamin C also reduces redox active transition metal ions in the active sites of specific biosynthetic enzymes.Ascorbic acid, or vitamin C, has the potential to protect both cytosolic and membrane components of cells from oxidant damage. In the cytosol, ascorbate acts as a primary antioxidant to scavenge free radical species that are generated as by-products of cellular metabolism. For cellular membranes, it may play an indirect antioxidant role to reduce the a-tocopheroxyl radical to a-tocopherol. The erythrocyte results indicate that ascorbate can interact directly with the plasma membrane as an antioxidant. Excellent sources of vitamin C include: parsley, broccoli, bell pepper, strawberries, oranges, lemon juice, papaya, cauliflower, kale, mustard greens.
Fig3. Structure of Ascorbate
Vitamin E (α-tocopherol):
Vitamin E (tocopherol) is a fat-soluble vitamin which functions solely as a membrane bound antioxidant that prevents cell membrane damage by inhibiting per oxidation of membrane phospholipids and disrupting free radical chain reactions induced by formation of lipid peroxides. Vitamin E also increases the bioavailability of vitamin A by inhibiting its intestinal oxidation . As the only membrane-bound lipid-soluble antioxidant, Vitamin E plays a key role in preventing cellular injury from oxidative stress associated with premature aging, cataracts, uncontrolled diabetes, cardiovascular disease, inflammation, and infection. Exogenous supplementation of functionally efficient antioxidants like vitamin E reactivates the enzymatic antioxidant system and guards against the insult caused by ROS during the pathogenesis of the diseases.Increased production of reactive oxygen species secondary to phagocyte respiratory burst occurs in pulmonary tuberculosis (TB) vitamin E and selenium supplementation reduces oxidative stress and enhances total antioxidant status in patients with pulmonary TB treated with standard chemotherapy. Vitamin E is found only in foods of plant origin. Wheat germ is the richest source of the vitamin. Vegetable oils and whole grains are additional rich sources of this nutrient. Nuts, peanut butter, salad dressings and vegetable oils are also good sources of vitamin E.
.
Fig4.The chemical structure of alpha-tocopherol
β-carotenoids:
Carotenoids are nature’s most widespread pigments and have also received substantial attention because of both their provitamin and antioxidant roles. More than 600 different carotenoids have been identified in nature. Carotenoids have a 40-carbon skeleton of isoprene units. The structure may be cyclized at one or both ends, may have various hydrogenation levels, or may possess oxygen-containing functional groups. Lycopene and ß-carotene are examples of acyclized and cyclized carotenoids, respectively. Carotenoid compounds most commonly occur in nature in the all-trans form. Mixtures of carotenoids or associations with others antioxidants (e.g. vitamin E) can increase their activity against free radicals. Carotenoids are found in colored fruits and vegetables. Apricots, antaloupe, carrots, pumpkin and sweet potato are sources of a-carotene and b-carotene; pink grapefruit, tomatoes and watermelon are sources of lycopene, z-carotene, b-carotene, phytofluene and phytoene. Mango, papaya, peaches, prunes, squash and oranges are sources of lutein, zeaxanthin, aand b-cryptoxanthin, a-, b- and z-carotene, phytofluene and phytoene, whereas green fruits and vegetables such as green beans, broccoli, brussel sprouts, cabbage, kale, kiwi, lettuce, peas and spinach are sources of lutein, zeaxanthin, a- and b-carotene. Carotenoid concentrations in fruits and vegetables vary with plant variety, degree of ripeness, time of harvest, and growing and storage conditions.
Fig5.Different types of Carotenoids
2.4.3NON NUTRIENTCOMPOUNDS:
Polyphenols - the potent antioxidants in plant foods:
Phenolic antioxidants, a specific group of secondary metabolites play the important role of protecting organism against harmful effects of oxygen radicals and other highly ROS. Their formation in human organisms is closely connected with the development of a wide range of degenerative diseases, mainly arteriosclerosis and other associated complications ,cancer and aging.Among natural antioxidants plant poly phenols play a very important role. Flavonoids are a class of poly phenolic compounds is widely and ubiquitously found in fruits , vegetables , grains ,nuts, and medicinal plants. High consumption of plant phenolics in the daily diet has been found to provide their ability to low density lipo proteins, platelet aggregation, growth of tumour cells and inflammation reactions. They are one of the major groups of nonessential dietary components appearing in vegetable foods. They are a wide chemical compounds group that are considered as secondary plant metabolites, with different activity and chemical structure,including more than 8,000 different compounds.
Fig6. Different Polyphenolic compounds
Flavonoids:
Flavonoids are a group of phenolic compounds with antioxidant activity that have been identified in fruits, vegetables, and other plant foods and that have been linked to reducing the risk of major chronic diseases. More than 4000 distinct flavonoids have been identified. Flavonols (quercetin, kaempferol, and myricetin), flavones (luteolin and apigenin), flavanols (catechin, epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate), flavanones (naringenin), anthocyanidins, and isoflavonoids (genistein) are common flavonoids in the diet. Flavonoids are most frequently found in nature as conjugates in glycosylated or esterified forms but can occur as aglycones, especially as a result of the effects of food processing.
Fig7.Types of Flavonoids
Phenolic acids:
Phenolic acids can be subdivided into two major groups, hydroxybenzoic acids and hydroxycinnamic acids .Hydroxybenzoic acid derivatives include p-hydroxybenzoic, protocatechuic, vannilic, syringic, and gallic acids. They are commonly present in the bound form and are typically a component of a complex structure like lignins and hydrolyzable tannins. They can also be found in the form of sugar derivatives and organic acids in plant foods. Food processing, such as thermal processing, pasteurization, fermentation, and freezing, contributes to the release of these bound phenolic acids Hydroxycinnamic acid derivatives include p-coumaric, caffeic, ferulic, and sinapic acids. They are mainly present in the bound form, linked to cell-wall structural components, such as cellulose, lignin, and proteins through ester bonds. Ferulic acids occur primarily in the seeds and leaves of plants, mainly covalently conjugated to mono- and disaccharides, plant-cell-wall polysaccharides, glycoproteins, polyamines, lignin, and insoluble carbohydrate biopolymers. Wheat bran is a good source of ferulic acids, which are esterified to hemicellulose of the cell walls. Free, soluble-conjugated, and bound ferulic acids in grains are present in the ratio of 0.1:1:100. Food processing, such as thermal processing, pasteurization, fermentation, and freezing, contributes to the release of these bound phenolic acids.
2.5ANTIOXIDANT ACTIVITY VERSUS ANTIOXIDANTS:
Due to the chemical diversity of antioxidant compounds present in foods, complete databases on food antioxidant content are not yet available. In addition, levels of single antioxidants in food do not necessarily reflect their total antioxidant capacity (TAC); this also depends on the synergic and redox interactions among the different molecules present in the food. The combined activity of the antioxidants in food or plasma is termed as AOA, which provides an integrated parameter rather than the simple sum of measurable antioxidants. In AOA the capacity of known and unknown antioxidants and their synergistic interaction is assessed, thus giving an insight into the delicate balance invivo, between oxidants, antioxidants, allied substances and metabolites.
Antioxidants react with radicals and other reactive species faster than biological substrates, thus protecting biological targets from oxidative damage. Further more the resulting anti oxidant radical possess high stability that is the antioxidant radical interrupts (rather than propagate) a chain reaction.
2.4. EXOGENOUS ANTIOXIDANT SYSTEM:
The body gets some of its antioxidants from the environment, more specifically from the food that is consumed (exogenous antioxidants). While the enzymatic antioxidants are intrinsic to the organism, the non-enzymatic components are both of intrinsic and exogenous nature. The non-enzymatic antioxidants consist of nutrient and non nutrient compounds.
2.4.1ENZYMATIC ANTIOXIDANTS:
Among the enzymatic antioxidants mainly three groups of enzymes play significant roles in protecting cells from oxidant stress:
Superoxide Dismutases (SOD) are enzymes that catalyze the conversion of two super oxides into hydrogen peroxide and oxygen. The benefit here is that hydrogen peroxide is substantially less toxic that superoxide. SOD accelerates this detoxifying reaction roughly 10,000-fold over the non-catalyzed reaction.
SODs are metal-containing enzymes that depend on bound manganese, copper or zinc for their antioxidant activity. In mammals, the manganese-containing enzyme is most abundant in mitochondria, while the zinc or copper forms predominant in cytoplasm. Interestingly, SODs are inducible enzymes - exposure of bacteria or vertebrate cells to higher concentrations of oxygen results in rapid increases in the concentration of SOD.
Catalase is found in peroxisomes in eucaryotic cells. It degrades hydrogen peroxide to water and oxygen, and hence finishes the detoxification reaction started by SOD.
Glutathione peroxidase is a group of enzymes, the most abundant of which contain selenium. These enzymes, like catalase, degrade hydrogen peroxide. They also reduce organic peroxides to alcohols, providing another route for eliminating toxic oxidants.In addition to these enzymes, glutathione transferase, ceruloplasmin, hemoxygenase and possibly several other enzymes may participate in enzymatic control of oxygen radicals and their products.
2.4.2NON –ENZYMATIC ANTIOXIDANTS:
NUTRIENT COMPOUNDS:
Vitamin C:
Ascorbate, an essential vitamin found in fruits and vegetables, has been particularly well studied in its role as an antioxidant and is suggested to serve several physiological functions including (1) preventing free-radical-induced damage to DNA, (2) quenching oxidants which can lead to the development of cataracts, (3) improving endothelial cell dysfunction, and (4) decreasing LDL induced leukocyte adhesion. Vitamin C readily scavenges reactive oxygen and nitrogen species and may thereby prevent oxidative damage to important biological macromolecules such as DNA, lipids, and proteins. Vitamin C also reduces redox active transition metal ions in the active sites of specific biosynthetic enzymes.Ascorbic acid, or vitamin C, has the potential to protect both cytosolic and membrane components of cells from oxidant damage. In the cytosol, ascorbate acts as a primary antioxidant to scavenge free radical species that are generated as by-products of cellular metabolism. For cellular membranes, it may play an indirect antioxidant role to reduce the a-tocopheroxyl radical to a-tocopherol. The erythrocyte results indicate that ascorbate can interact directly with the plasma membrane as an antioxidant. Excellent sources of vitamin C include: parsley, broccoli, bell pepper, strawberries, oranges, lemon juice, papaya, cauliflower, kale, mustard greens.
Fig3. Structure of Ascorbate
Vitamin E (α-tocopherol):
Vitamin E (tocopherol) is a fat-soluble vitamin which functions solely as a membrane bound antioxidant that prevents cell membrane damage by inhibiting per oxidation of membrane phospholipids and disrupting free radical chain reactions induced by formation of lipid peroxides. Vitamin E also increases the bioavailability of vitamin A by inhibiting its intestinal oxidation . As the only membrane-bound lipid-soluble antioxidant, Vitamin E plays a key role in preventing cellular injury from oxidative stress associated with premature aging, cataracts, uncontrolled diabetes, cardiovascular disease, inflammation, and infection. Exogenous supplementation of functionally efficient antioxidants like vitamin E reactivates the enzymatic antioxidant system and guards against the insult caused by ROS during the pathogenesis of the diseases.Increased production of reactive oxygen species secondary to phagocyte respiratory burst occurs in pulmonary tuberculosis (TB) vitamin E and selenium supplementation reduces oxidative stress and enhances total antioxidant status in patients with pulmonary TB treated with standard chemotherapy. Vitamin E is found only in foods of plant origin. Wheat germ is the richest source of the vitamin. Vegetable oils and whole grains are additional rich sources of this nutrient. Nuts, peanut butter, salad dressings and vegetable oils are also good sources of vitamin E.
.
Fig4.The chemical structure of alpha-tocopherol
β-carotenoids:
Carotenoids are nature’s most widespread pigments and have also received substantial attention because of both their provitamin and antioxidant roles. More than 600 different carotenoids have been identified in nature. Carotenoids have a 40-carbon skeleton of isoprene units. The structure may be cyclized at one or both ends, may have various hydrogenation levels, or may possess oxygen-containing functional groups. Lycopene and ß-carotene are examples of acyclized and cyclized carotenoids, respectively. Carotenoid compounds most commonly occur in nature in the all-trans form. Mixtures of carotenoids or associations with others antioxidants (e.g. vitamin E) can increase their activity against free radicals. Carotenoids are found in colored fruits and vegetables. Apricots, antaloupe, carrots, pumpkin and sweet potato are sources of a-carotene and b-carotene; pink grapefruit, tomatoes and watermelon are sources of lycopene, z-carotene, b-carotene, phytofluene and phytoene. Mango, papaya, peaches, prunes, squash and oranges are sources of lutein, zeaxanthin, aand b-cryptoxanthin, a-, b- and z-carotene, phytofluene and phytoene, whereas green fruits and vegetables such as green beans, broccoli, brussel sprouts, cabbage, kale, kiwi, lettuce, peas and spinach are sources of lutein, zeaxanthin, a- and b-carotene. Carotenoid concentrations in fruits and vegetables vary with plant variety, degree of ripeness, time of harvest, and growing and storage conditions.
Fig5.Different types of Carotenoids
2.4.3NON NUTRIENTCOMPOUNDS:
Polyphenols - the potent antioxidants in plant foods:
Phenolic antioxidants, a specific group of secondary metabolites play the important role of protecting organism against harmful effects of oxygen radicals and other highly ROS. Their formation in human organisms is closely connected with the development of a wide range of degenerative diseases, mainly arteriosclerosis and other associated complications ,cancer and aging.Among natural antioxidants plant poly phenols play a very important role. Flavonoids are a class of poly phenolic compounds is widely and ubiquitously found in fruits , vegetables , grains ,nuts, and medicinal plants. High consumption of plant phenolics in the daily diet has been found to provide their ability to low density lipo proteins, platelet aggregation, growth of tumour cells and inflammation reactions. They are one of the major groups of nonessential dietary components appearing in vegetable foods. They are a wide chemical compounds group that are considered as secondary plant metabolites, with different activity and chemical structure,including more than 8,000 different compounds.
Fig6. Different Polyphenolic compounds
Flavonoids:
Flavonoids are a group of phenolic compounds with antioxidant activity that have been identified in fruits, vegetables, and other plant foods and that have been linked to reducing the risk of major chronic diseases. More than 4000 distinct flavonoids have been identified. Flavonols (quercetin, kaempferol, and myricetin), flavones (luteolin and apigenin), flavanols (catechin, epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate), flavanones (naringenin), anthocyanidins, and isoflavonoids (genistein) are common flavonoids in the diet. Flavonoids are most frequently found in nature as conjugates in glycosylated or esterified forms but can occur as aglycones, especially as a result of the effects of food processing.
Fig7.Types of Flavonoids
Phenolic acids:
Phenolic acids can be subdivided into two major groups, hydroxybenzoic acids and hydroxycinnamic acids .Hydroxybenzoic acid derivatives include p-hydroxybenzoic, protocatechuic, vannilic, syringic, and gallic acids. They are commonly present in the bound form and are typically a component of a complex structure like lignins and hydrolyzable tannins. They can also be found in the form of sugar derivatives and organic acids in plant foods. Food processing, such as thermal processing, pasteurization, fermentation, and freezing, contributes to the release of these bound phenolic acids Hydroxycinnamic acid derivatives include p-coumaric, caffeic, ferulic, and sinapic acids. They are mainly present in the bound form, linked to cell-wall structural components, such as cellulose, lignin, and proteins through ester bonds. Ferulic acids occur primarily in the seeds and leaves of plants, mainly covalently conjugated to mono- and disaccharides, plant-cell-wall polysaccharides, glycoproteins, polyamines, lignin, and insoluble carbohydrate biopolymers. Wheat bran is a good source of ferulic acids, which are esterified to hemicellulose of the cell walls. Free, soluble-conjugated, and bound ferulic acids in grains are present in the ratio of 0.1:1:100. Food processing, such as thermal processing, pasteurization, fermentation, and freezing, contributes to the release of these bound phenolic acids.
2.5ANTIOXIDANT ACTIVITY VERSUS ANTIOXIDANTS:
Due to the chemical diversity of antioxidant compounds present in foods, complete databases on food antioxidant content are not yet available. In addition, levels of single antioxidants in food do not necessarily reflect their total antioxidant capacity (TAC); this also depends on the synergic and redox interactions among the different molecules present in the food. The combined activity of the antioxidants in food or plasma is termed as AOA, which provides an integrated parameter rather than the simple sum of measurable antioxidants. In AOA the capacity of known and unknown antioxidants and their synergistic interaction is assessed, thus giving an insight into the delicate balance invivo, between oxidants, antioxidants, allied substances and metabolites.
Scientists identify human body's natural defenses against cancer
Researchers in Canada have identified a novel molecular mechanism that prevents cancer.
Researchers from the Universite de Montreal and the Universite de Sherbrooke have found that the SOCS1 molecule prevents the cancer-causing activity of cytokines, hormones that are culprits in cancer-prone chronic inflammation diseases such as Crohns, in smokers and people exposed to asbestos.
"Excessive cytokine activity promotes cancer," said Dr. Gerardo Ferbeyre, senior author and a Universite de Montreal biochemistry professor.
"Discovery of these mechanisms will enable scientists to design a cancer-prevention strategy for people with chronic inflammatory diseases and lead to better understanding of the human body's natural defenses against cancer," Ferbeyre added.
The researchers say they were surprised to find that SOCS1 is linked to p53, the master regulator of natural anticancer defenses.
"Our team showed that SOCS1 is a direct regulator of the p53 gene and that in its absence the p53 pathway is significantly disabled," said Ferbeyre, noting the p53 gene is frequently lost in human cancer patients as it is SOCS1.
The new research suggests that the effects of SOCS1 loss in patients might also disable the p53 tumour suppression pathway.
The researchers also showed that the reintroduction of SOCS1 into tumour cells locked them into a permanent dormant state known as cell senescence preventing them from multiplying wildly as is typical of cancer cells.
"With this study, we provide new hope of finding a treatment to activate natural anticancer defenses in people at risk of suffering from cancer prompted by chronic inflammation," Ferbeyre said.
The research has been published in the prestigious journal Molecular Cell. (ANI)
Researchers from the Universite de Montreal and the Universite de Sherbrooke have found that the SOCS1 molecule prevents the cancer-causing activity of cytokines, hormones that are culprits in cancer-prone chronic inflammation diseases such as Crohns, in smokers and people exposed to asbestos.
"Excessive cytokine activity promotes cancer," said Dr. Gerardo Ferbeyre, senior author and a Universite de Montreal biochemistry professor.
"Discovery of these mechanisms will enable scientists to design a cancer-prevention strategy for people with chronic inflammatory diseases and lead to better understanding of the human body's natural defenses against cancer," Ferbeyre added.
The researchers say they were surprised to find that SOCS1 is linked to p53, the master regulator of natural anticancer defenses.
"Our team showed that SOCS1 is a direct regulator of the p53 gene and that in its absence the p53 pathway is significantly disabled," said Ferbeyre, noting the p53 gene is frequently lost in human cancer patients as it is SOCS1.
The new research suggests that the effects of SOCS1 loss in patients might also disable the p53 tumour suppression pathway.
The researchers also showed that the reintroduction of SOCS1 into tumour cells locked them into a permanent dormant state known as cell senescence preventing them from multiplying wildly as is typical of cancer cells.
"With this study, we provide new hope of finding a treatment to activate natural anticancer defenses in people at risk of suffering from cancer prompted by chronic inflammation," Ferbeyre said.
The research has been published in the prestigious journal Molecular Cell. (ANI)
Friday, December 11, 2009
ANTIOXIDENTS
DEFINITION:
Antioxidants are often described as “free radical scavengers” meaning that they neutralize the electrical charge and prevent the free radicals from taking electrons from other molecules. They play a key role in the body defense system against reactive oxygen species (ROS) which are known to be involved in the pathogenesis of aging and many degenerative diseases such as cardiovascular diseases,cataract and cancers atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing.
To protect the cells and organ systems of the body against reactive oxygen species, humans have evolved a highly sophisticated and complex antioxidant protection system. It involves a variety of components, both endogenous and exogenous in origin, that function interactively and synergistically to neutralize free radicals. These components include:
ANTIOXIDENTS IN ANIMALS
Endogenous Antioxidants
• Bilirubin
• Thiols, e.g., glutathione, lipoic acid, N-acetyl cysteine
• NADPH and NADH
• Ubiquinone (coenzyme Q10)
• Uric acid
• Enzymes:
– copper/zinc and manganese-dependent superoxide
dismutase (SOD)
– iron-dependent catalase
– selenium-dependent glutathione peroxidase
Dietary Antioxidants
• Vitamin C
• Vitamin E
• Beta carotene and other carotenoids and oxycarotenoids,
e.g., lycopene and lutein
• Polyphenols, e.g., flavonoids, flavones, flavonols, and
proanthocyanidins
Metal Binding Proteins
• Albumin (copper)
• Ceruloplasmin (copper)
• Metallothionein (copper)
• Ferritin (iron)
• Myoglobin (iron)
• Transferrin (iron)
There are two lines of antioxidant defense within the cell. The first line, found in the fat soluble cellular membrane consists of vitamin E, beta-carotene, and coenzyme Q. Of these, vitamin E is considered the most potent chain breaking antioxidant within the membrane of the cell. Inside the cell, water soluble antioxidant scavengers are present. These include vitamin C, glutathione peroxidase, superoxide dismutase (SOD), and catalase .
Plant cells are known to have both enzymatic and non-enzymatic defense mechanisms to counteract the destructive effects of activated oxygen species. The antioxidant defense system consists of low molecular weight antioxidants such as ascorbate, glutathione, a-tocopherol and b-carotenoids, peptides, vitamins, flavonoids, phenolic acids, alkaloids as well as several antioxidant enzymes such as superoxide dismutase (SOD), guaiacol peroxidase (POD), ascorbic acid peroxidase (APX) and glutathione reductase (GR)
ANTIONIDNTS IN PLANTS
ENZYMATIC:
Oxido reductase
Catalases
superoxide dismutases
guaiacol peroxidase (POD),
ascorbic acid peroxidase (APX)
glutathione reductase.
Non-enzymatic:
Nutrient:
ascorbate
glutathione
a-tocopherol
b-carotenoids
Non-nutrient:
Flavonoids
Phenolic acids
Alkaloids
BHA (butylated hydroxyanisole)
BHT (butylated hydroxytoluene).
Antioxidants are often described as “free radical scavengers” meaning that they neutralize the electrical charge and prevent the free radicals from taking electrons from other molecules. They play a key role in the body defense system against reactive oxygen species (ROS) which are known to be involved in the pathogenesis of aging and many degenerative diseases such as cardiovascular diseases,cataract and cancers atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing.
To protect the cells and organ systems of the body against reactive oxygen species, humans have evolved a highly sophisticated and complex antioxidant protection system. It involves a variety of components, both endogenous and exogenous in origin, that function interactively and synergistically to neutralize free radicals. These components include:
ANTIOXIDENTS IN ANIMALS
Endogenous Antioxidants
• Bilirubin
• Thiols, e.g., glutathione, lipoic acid, N-acetyl cysteine
• NADPH and NADH
• Ubiquinone (coenzyme Q10)
• Uric acid
• Enzymes:
– copper/zinc and manganese-dependent superoxide
dismutase (SOD)
– iron-dependent catalase
– selenium-dependent glutathione peroxidase
Dietary Antioxidants
• Vitamin C
• Vitamin E
• Beta carotene and other carotenoids and oxycarotenoids,
e.g., lycopene and lutein
• Polyphenols, e.g., flavonoids, flavones, flavonols, and
proanthocyanidins
Metal Binding Proteins
• Albumin (copper)
• Ceruloplasmin (copper)
• Metallothionein (copper)
• Ferritin (iron)
• Myoglobin (iron)
• Transferrin (iron)
There are two lines of antioxidant defense within the cell. The first line, found in the fat soluble cellular membrane consists of vitamin E, beta-carotene, and coenzyme Q. Of these, vitamin E is considered the most potent chain breaking antioxidant within the membrane of the cell. Inside the cell, water soluble antioxidant scavengers are present. These include vitamin C, glutathione peroxidase, superoxide dismutase (SOD), and catalase .
Plant cells are known to have both enzymatic and non-enzymatic defense mechanisms to counteract the destructive effects of activated oxygen species. The antioxidant defense system consists of low molecular weight antioxidants such as ascorbate, glutathione, a-tocopherol and b-carotenoids, peptides, vitamins, flavonoids, phenolic acids, alkaloids as well as several antioxidant enzymes such as superoxide dismutase (SOD), guaiacol peroxidase (POD), ascorbic acid peroxidase (APX) and glutathione reductase (GR)
ANTIONIDNTS IN PLANTS
ENZYMATIC:
Oxido reductase
Catalases
superoxide dismutases
guaiacol peroxidase (POD),
ascorbic acid peroxidase (APX)
glutathione reductase.
Non-enzymatic:
Nutrient:
ascorbate
glutathione
a-tocopherol
b-carotenoids
Non-nutrient:
Flavonoids
Phenolic acids
Alkaloids
BHA (butylated hydroxyanisole)
BHT (butylated hydroxytoluene).
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