Biochemical studies suggest that oxidation may be important in a number of brain pathologies. The few epidemiological studies are consistent with a protective effect of fruits and vegetables or antioxidants in a number of neurological pathologies, including brain ischemia, Parkinsons disease (PD), and familial amyotrophic lateral sclerosis (FALS), a degenerative disorder of motor neurons .
Ischemic episodes liberate iron, an important catalyst in oxygen radical forming reactions; iron chelators reduce neuron loss following this trauma. In individuals suffering from Parkinson's disease, oxidative DNA damaged is elevated within brain regions rich in dopaminergic neurons (E. Övervik, J. Sanchez-Ramos and B. Ames, unpublished). The most convincing evidence so far for a link between neurological disorders and oxygen radical formation is the strong association found between FALS and mutations in the Cu/Zn superoxide dismutase gene, suggesting that oxygen radicals might be responsible for the selective degeneration of motor neurons occurring in this fatal disease.
The protective role of superoxide dismutase against brain injury due to ischemia is supported by the finding that its overproduction is protective in a transgenic mouse model. Based on the similar protective effects against ischemia induced brain injury by inhibition of nitric oxide formation, and the recent evidence implicating these two radical species in cytotoxicity of neuronal cells, it would appear that peroxynitrite, a powerful oxidant formed from the combination of superoxide anion radical and nitric oxide, plays an important role in neuronal injury following ischemia and reperfusion.
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Tuesday, February 12, 2008
Antioxidants and Cataracts
Cataract removal is the most common operation in the U.S. (1.2 million per year) with costs of over 3 billion dollars.
Taylor has recently reviewed the impressive evidence that cataracts have an oxidative etiology and that dietary antioxidants can prevent their formation in humans. Five epidemiological studies that have examined the effect of dietary antioxidants on cataracts show strong preventative effects of ascorbate, tocopherol, and carotenoids. Those individuals taking daily supplements of ascorbate or tocopherol had about one-third the risk.
Smoking, a severe oxidative stress, is a major risk factor for cataracts and radiation, an oxidative mutagen, is well-known to cause cataracts.
Eye proteins show an increased level of methionine sulfoxide with age and proteins in human cataracts have over 60 percent of their methionine residues oxidized. Pregnant mice depleted of Glutathione, the main sulfhydryl antioxidants in cells, produce offspring with cataracts. The most promising preventative strategy against cataracts appears to be to increase dietary antioxidants and to decrease smoking.
Click here for more about Glutathione and its benefits to our body.
Taylor has recently reviewed the impressive evidence that cataracts have an oxidative etiology and that dietary antioxidants can prevent their formation in humans. Five epidemiological studies that have examined the effect of dietary antioxidants on cataracts show strong preventative effects of ascorbate, tocopherol, and carotenoids. Those individuals taking daily supplements of ascorbate or tocopherol had about one-third the risk.
Smoking, a severe oxidative stress, is a major risk factor for cataracts and radiation, an oxidative mutagen, is well-known to cause cataracts.
Eye proteins show an increased level of methionine sulfoxide with age and proteins in human cataracts have over 60 percent of their methionine residues oxidized. Pregnant mice depleted of Glutathione, the main sulfhydryl antioxidants in cells, produce offspring with cataracts. The most promising preventative strategy against cataracts appears to be to increase dietary antioxidants and to decrease smoking.
Click here for more about Glutathione and its benefits to our body.
Monday, February 11, 2008
Antioxidants, and the Immune System
The proliferation of T and B cells, natural killer cells, and lymphokine activated killer cells that are required to mount an effective defense against pathogens and tumor cells appear to be inhibited markedly with age and upon exposure to oxidants. These effects can, in part, be counteracted in elderly individuals by dietary antioxidant supplementation. While the endogenous sources of oxidants that lead to the suppression of lymphocyte dependent immunity are not known, in vitro studies have demonstrated that polymorphonuclear leucocytes and macrophages, both can inhibit proliferation of various lymphocyte subpopulations through the production of reactive oxygen intermediates and the prostaglandin metabolite PGE2 as well as from nitric oxide.
This suggests that conditions that involve infiltration of polymorphonuclear leucocytes and macrophages (i.e., chronic inflammatory diseases), could result in compromised lymphocyte function. The suppressive effects of macrophages on mitogen induced lymphocyte proliferation can be reversed partially by thiol reagents, catalase or indomethacin, or by NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide synthesis.
The age associated decrease in cell mediated immunity may be due to a decreased level of certain small molecule antioxidant and antioxidant enzymes that accompany the aging process.
Calorie restriction, a dietary regimen that increases maximal lifespan in rodents also enhances T lymphocyte responsiveness possibly by slowing the rate of thymus involution and by boosting the level of cellular antioxidant defenses.
This suggests that conditions that involve infiltration of polymorphonuclear leucocytes and macrophages (i.e., chronic inflammatory diseases), could result in compromised lymphocyte function. The suppressive effects of macrophages on mitogen induced lymphocyte proliferation can be reversed partially by thiol reagents, catalase or indomethacin, or by NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide synthesis.
The age associated decrease in cell mediated immunity may be due to a decreased level of certain small molecule antioxidant and antioxidant enzymes that accompany the aging process.
Calorie restriction, a dietary regimen that increases maximal lifespan in rodents also enhances T lymphocyte responsiveness possibly by slowing the rate of thymus involution and by boosting the level of cellular antioxidant defenses.
Antioxidants and cardiovascular disease
A major development in cardiovascular disease research is the finding that oxidation reactions play a central role in atherogenesis and that in epidemiological studies cardiovascular disease is associated with low plasma concentrations of ascorbate, tocopherol and ß-carotene.
A wealth of evidence suggests that oxidative modification of apolipoprotein B100 plays a key role in LDL recognition and that LDL uptake by scavenger receptors in macrophages leads to foam cell formation and atheroschlerotic plaques.
Apolipoprotein B100 can be altered by reactive products of lipid peroxidation that causes a net decrease in positive charge, a modification that leads to its recognition by the scavenger receptors. The beneficial effects of dietary Antioxidants is also strengthened by animal and biochemical studies.
Click here for more about Glutathione and its benefits to our body.
A wealth of evidence suggests that oxidative modification of apolipoprotein B100 plays a key role in LDL recognition and that LDL uptake by scavenger receptors in macrophages leads to foam cell formation and atheroschlerotic plaques.
Apolipoprotein B100 can be altered by reactive products of lipid peroxidation that causes a net decrease in positive charge, a modification that leads to its recognition by the scavenger receptors. The beneficial effects of dietary Antioxidants is also strengthened by animal and biochemical studies.
Click here for more about Glutathione and its benefits to our body.
Antioxidants and Cancer
A critical factor in mutagenesis is cell division. When the cell divides, an unrepaired DNA lesion can give rise to a mutation. Thus an important factor in mutagenesis, and therefore carcinogenesis, is the cell division rate in the precursors of tumor cells. Stem cells are important as precursor cells in cancer because they are not on their way to being discarded. Increasing their cell division rate would increase mutation. As expected, there is little cancer in non-dividing cells. Such diverse agents as chronic infection high levels of particular hormones, or chemicals at doses that cause cell death result in increased cell division and therefore an increased risk for cancer.
Oxidants form one important class of agents that stimulate cell division. This may be related to the stimulation of cell division that occurs during the inflammatory process accompanying wound healing. Antioxidants therefore can decrease mutagenesis, and thus carcinogenesis, in two ways:
by decreasing oxidative DNA damage and by decreasing cell division. Of great interest is the understanding of mechanisms by which tocopherol and carotenoids can prevent cell division
There is an increasing literature on the protective role of dietary tocopherol, ascorbate, and ß-carotene in lowering the incidence of a wide variety of human cancer.
Antioxidants can counteract the induction of cancer in rodents by a variety of carcinogens. Two of the major causes of cancer, cigarette smoke and chronic inflammation, both appear to involve oxidants in their mechanism of action.
Almost all of the epidemiological studies that examined the relation between Antioxidant levels and cigarette-induced lung cancer showed a statistically significant protective effect of Antioxidants.
Antioxidants inhibit much of the pathology of cigarette smoke in rodents.
Inflammatory reactions release large amounts of NO, a radical, nitrosating agent, and indirect mutagenic oxidant. Ascorbate inhibits nitrosation under physiological conditions.
Antioxidants help to protect against the carcinogenic effects of chronic inflammation, as discussed above.
Click here for more about Glutathione and its benefits to our body.
Oxidants form one important class of agents that stimulate cell division. This may be related to the stimulation of cell division that occurs during the inflammatory process accompanying wound healing. Antioxidants therefore can decrease mutagenesis, and thus carcinogenesis, in two ways:
by decreasing oxidative DNA damage and by decreasing cell division. Of great interest is the understanding of mechanisms by which tocopherol and carotenoids can prevent cell division
There is an increasing literature on the protective role of dietary tocopherol, ascorbate, and ß-carotene in lowering the incidence of a wide variety of human cancer.
Antioxidants can counteract the induction of cancer in rodents by a variety of carcinogens. Two of the major causes of cancer, cigarette smoke and chronic inflammation, both appear to involve oxidants in their mechanism of action.
Almost all of the epidemiological studies that examined the relation between Antioxidant levels and cigarette-induced lung cancer showed a statistically significant protective effect of Antioxidants.
Antioxidants inhibit much of the pathology of cigarette smoke in rodents.
Inflammatory reactions release large amounts of NO, a radical, nitrosating agent, and indirect mutagenic oxidant. Ascorbate inhibits nitrosation under physiological conditions.
Antioxidants help to protect against the carcinogenic effects of chronic inflammation, as discussed above.
Click here for more about Glutathione and its benefits to our body.
Dietary antioxidants
The effect of dietary intake of the antioxidants ascorbate, tocopherol, and carotenoids is difficult to disentangle by epidemiological studies from other important vitamins and ingredients in fruits and vegetables.
Nevertheless, several arguments suggest that the antioxidants content of fruits and vegetables is a major contributor to their protective effect.
1) Biochemical data, discussed above shows that oxidative damage is massive and is likely to be the major endogenous damage to DNA, proteins, and lipids.
2) Studies showing that oxidative damage to sperm DNA is increased when dietary ascorbate is insufficient
3) Epidemiological studies and intervention trials on prevention of cancer and heart disease in people taking antioxidants supplements are suggestive, though larger studies need to be done. Clinical trials using antioxidants will be the critical test for many of the ideas.
4) Studies on oxidative mechanisms and epidemiology on antioxidants protection for individual degenerative diseases.
Small molecule dietary antioxidants such as Vitamin C (ascorbate), Vitamin E (tocopherol), and carotenoids have generated particular interest as anticarcinogens and as defenses against degenerative diseases. Most carotenoids have antioxidants activity, particularly against singlet oxygen and many, including ß-carotene, can be metabolized to Vitamin A (retinal)
We have called attention to a number of previously neglected physiological antioxidants including urate, bilirubin, carnosine, and ubiquinol. Ubiquinone (CoQ10), for example, is the critical small molecule for transporting electrons in mitochondria for the generation of energy. Its reduced form, ubiquinol, is an effective antioxidants in membranes.
Optimal levels of dietary ubiquinone/ubiquinol could be of importance in many of the
degenerative diseases.
Click here for more about Glutathione and its benefits to our body.
Nevertheless, several arguments suggest that the antioxidants content of fruits and vegetables is a major contributor to their protective effect.
1) Biochemical data, discussed above shows that oxidative damage is massive and is likely to be the major endogenous damage to DNA, proteins, and lipids.
2) Studies showing that oxidative damage to sperm DNA is increased when dietary ascorbate is insufficient
3) Epidemiological studies and intervention trials on prevention of cancer and heart disease in people taking antioxidants supplements are suggestive, though larger studies need to be done. Clinical trials using antioxidants will be the critical test for many of the ideas.
4) Studies on oxidative mechanisms and epidemiology on antioxidants protection for individual degenerative diseases.
Small molecule dietary antioxidants such as Vitamin C (ascorbate), Vitamin E (tocopherol), and carotenoids have generated particular interest as anticarcinogens and as defenses against degenerative diseases. Most carotenoids have antioxidants activity, particularly against singlet oxygen and many, including ß-carotene, can be metabolized to Vitamin A (retinal)
We have called attention to a number of previously neglected physiological antioxidants including urate, bilirubin, carnosine, and ubiquinol. Ubiquinone (CoQ10), for example, is the critical small molecule for transporting electrons in mitochondria for the generation of energy. Its reduced form, ubiquinol, is an effective antioxidants in membranes.
Optimal levels of dietary ubiquinone/ubiquinol could be of importance in many of the
degenerative diseases.
Click here for more about Glutathione and its benefits to our body.
Antioxidants Protect Against Disease
Many defense mechanisms within the organism have evolved to limit the levels of reactive oxidants and the damage they inflict. Among the defenses are enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. The glutathione S-transferases inactivate reactive electrophilic mutagens, including the aldehyde products of lipid peroxidation.
There are also many structural defenses such as sequestering H202 generating enzymes in peroxisomes and chelating any free iron or copper salts in transferrin and ferritin or ceruloplasmin to avoid Fenton chemistry. Superoxide, however, can release iron from ferritin.
Oxidized DNA is repaired by a series of glycosylases that are specific for particular oxidized bases and possibly by non-specific excision repair enzymes. In the absence of cell division these oxidative lesions are removed from DNA quite effectively and the mutation rate is kept to a minimum. Oxidized proteins are degraded by proteases. Lipid hydroperoxides are destroyed by glutathione peroxidase.
Almost all of these defenses appear to be inducible, as are most other types of defenses, i.e., the amounts increase in response to damage. There is a large literature showing that cells respond to low levels of radiation, an oxidative mutagen, by inducing antioxidant defenses that help to protect them against mutation by high levels of radiation.
There is a tradeoff however, since the induction of these defenses makes the cell more sensitive to alkylating mutagens.
In addition to the protective effects of endogenous enzymatic antioxidant defenses, consumption of dietary antioxidants appears to be of great importance. Fruits and vegetables, the main source of antioxidants in the diet, are associated with a lowered risk of degenerative diseases. Block and her colleagues have recently reviewed 172 studies in the epidemiological literature that relate, with great consistency, the lack of adequate consumption of fruits and vegetables to cancer incidence.
The quarter of the population with low dietary intake of fruits and vegetables compared to the quarter with high intake has double the cancer rate for most types of cancer (lung, larynx, oral cavity, esophagus, stomach, colon and rectum, bladder, pancreas, cervix, and ovary). Data on the types of cancer known to be associated with hormone levels are not as consistent and show less protection by fruits and vegetables: for breast cancer the protective effect was about 30%. There is also literature on the protective effect of fruit and vegetable consumption on heart disease and stroke. Only 9% of Americans eat five servings of fruits and vegetables per day, the intake recommended by the National Cancer Insitute and the National Research Council. European countries with low fruit and vegetable intake (e.g., Scotland) are generally in poorer health and have higher rates of heart disease and cancer than countries with high intake (e.g., Greece).
The cost of fruits and vegetables is an important factor in discouraging consumption. Poorer people spend a higher percentage of their income on food, eat less fruits and vegetables, and have shorter life expectancy than wealthier people. A major contributor to health in this century was synthetic pesticides which markedly decreased the cost of food production and ensured that most of the crops planted would be eaten by humans rather than insects. Synthetic pesticide residues do not appear to be a significant cause of cancer.
Click here for more about Glutathione and its benefits to our body.
There are also many structural defenses such as sequestering H202 generating enzymes in peroxisomes and chelating any free iron or copper salts in transferrin and ferritin or ceruloplasmin to avoid Fenton chemistry. Superoxide, however, can release iron from ferritin.
Oxidized DNA is repaired by a series of glycosylases that are specific for particular oxidized bases and possibly by non-specific excision repair enzymes. In the absence of cell division these oxidative lesions are removed from DNA quite effectively and the mutation rate is kept to a minimum. Oxidized proteins are degraded by proteases. Lipid hydroperoxides are destroyed by glutathione peroxidase.
Almost all of these defenses appear to be inducible, as are most other types of defenses, i.e., the amounts increase in response to damage. There is a large literature showing that cells respond to low levels of radiation, an oxidative mutagen, by inducing antioxidant defenses that help to protect them against mutation by high levels of radiation.
There is a tradeoff however, since the induction of these defenses makes the cell more sensitive to alkylating mutagens.
In addition to the protective effects of endogenous enzymatic antioxidant defenses, consumption of dietary antioxidants appears to be of great importance. Fruits and vegetables, the main source of antioxidants in the diet, are associated with a lowered risk of degenerative diseases. Block and her colleagues have recently reviewed 172 studies in the epidemiological literature that relate, with great consistency, the lack of adequate consumption of fruits and vegetables to cancer incidence.
The quarter of the population with low dietary intake of fruits and vegetables compared to the quarter with high intake has double the cancer rate for most types of cancer (lung, larynx, oral cavity, esophagus, stomach, colon and rectum, bladder, pancreas, cervix, and ovary). Data on the types of cancer known to be associated with hormone levels are not as consistent and show less protection by fruits and vegetables: for breast cancer the protective effect was about 30%. There is also literature on the protective effect of fruit and vegetable consumption on heart disease and stroke. Only 9% of Americans eat five servings of fruits and vegetables per day, the intake recommended by the National Cancer Insitute and the National Research Council. European countries with low fruit and vegetable intake (e.g., Scotland) are generally in poorer health and have higher rates of heart disease and cancer than countries with high intake (e.g., Greece).
The cost of fruits and vegetables is an important factor in discouraging consumption. Poorer people spend a higher percentage of their income on food, eat less fruits and vegetables, and have shorter life expectancy than wealthier people. A major contributor to health in this century was synthetic pesticides which markedly decreased the cost of food production and ensured that most of the crops planted would be eaten by humans rather than insects. Synthetic pesticide residues do not appear to be a significant cause of cancer.
Click here for more about Glutathione and its benefits to our body.
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