Smoking, which we and others argue is a major oxidative stress in addition to a source of mutagens, contributes to about one-third of U.S. cancer, about one-quarter of U.S. heart disease and, about 400,000 premature deaths per year in the U.S..
Tobacco is a major global cause of cancer, but it causes even more deaths by other diseases. Tobacco will cause about 3 million deaths per year worldwide in the l990s and will, at present rates of smoking, cause about l0 million deaths per year a few decades from now.
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Showing posts with label heart disease. Show all posts
Showing posts with label heart disease. Show all posts
Monday, February 11, 2008
Thursday, February 7, 2008
Sources and Effects of Oxidants
Four endogenous sources appear to account for most of the oxidants produced by cells:
1) As a consequence of normal aerobic respiration, mitochondria consume molecular oxygen, reducing it by sequential steps to produce H20. Inevitable by-products of this process, as stated above, are O2.-, H202, and .OH. About l012 oxygen molecules are processed by each rat cell daily, and the leakage of partially reduced oxygen molecules is about 2%, yielding about 2x1010 superoxide and hydrogen peroxide molecules per cell per day.
2) Phagocytic cells destroy bacteria or virus-infected cells with an oxidative burst of NO, O2.-, H2O2, and [[macron]]OCl. Chronic infection by viruses, bacteria, or parasites, results in a chronic phagocytic activity and consequent chronic inflammation, which is a major risk factor for cancer. Chronic infections are particularly prevalent in third world countries.
3) Peroxisomes, which are organelles responsible for degrading fatty acids and other molecules, produce H202 as a byproduct, which is then degraded by catalase. Evidence suggests that, under certain conditions, some of the peroxide escapes degradation, resulting in its release into other compartments of the cell and in increased oxidative DNA damage.
4) Cytochrome P450 enzymes in animals constitute one of the primary defense systems against natural toxic chemicals from plants, the major source of dietary toxins. The induction of these enzymes, prevent acute toxic effects from foreign chemicals, but also results in oxidant by-products that damage DNA (Park, J.-Y. K. and Ames, B.N., unpublished).
Click here for more about Glutathione and its benefits to our body.
Three exogenous sources may significantly increase the large endogenous oxidant load.
1) The oxides of nitrogen (NOx) in cigarette smoke (about 1000 ppm) cause oxidation of macromolecules, and deplete antioxidant levels. This is likely to contribute significantly to the pathology of smoking. Smoking is a risk factor for heart disease as well as a wide variety of cancers in addition to lung cancer.
2) Iron (and copper) salts promote the generation of oxidizing radicals from peroxides (Fenton chemistry). Men who absorb significantly more than normal amounts of dietary iron due to a genetic defect (hemochromatosis disease) are at an increased risk for both cancer and heart disease. It has therefore been argued that too much dietary copper or iron, particularly heme iron (which is high in meat), is a risk factor for cardiovascular disease and cancer in normal men
3) Normal diets contain plant food with large amounts of natural phenolic compounds, such as chlorogenic and caffeic acid, that may generate oxidants by redox cycling .
Click here for more about Glutathione and its benefits to our body.
1) As a consequence of normal aerobic respiration, mitochondria consume molecular oxygen, reducing it by sequential steps to produce H20. Inevitable by-products of this process, as stated above, are O2.-, H202, and .OH. About l012 oxygen molecules are processed by each rat cell daily, and the leakage of partially reduced oxygen molecules is about 2%, yielding about 2x1010 superoxide and hydrogen peroxide molecules per cell per day.
2) Phagocytic cells destroy bacteria or virus-infected cells with an oxidative burst of NO, O2.-, H2O2, and [[macron]]OCl. Chronic infection by viruses, bacteria, or parasites, results in a chronic phagocytic activity and consequent chronic inflammation, which is a major risk factor for cancer. Chronic infections are particularly prevalent in third world countries.
3) Peroxisomes, which are organelles responsible for degrading fatty acids and other molecules, produce H202 as a byproduct, which is then degraded by catalase. Evidence suggests that, under certain conditions, some of the peroxide escapes degradation, resulting in its release into other compartments of the cell and in increased oxidative DNA damage.
4) Cytochrome P450 enzymes in animals constitute one of the primary defense systems against natural toxic chemicals from plants, the major source of dietary toxins. The induction of these enzymes, prevent acute toxic effects from foreign chemicals, but also results in oxidant by-products that damage DNA (Park, J.-Y. K. and Ames, B.N., unpublished).
Click here for more about Glutathione and its benefits to our body.
Three exogenous sources may significantly increase the large endogenous oxidant load.
1) The oxides of nitrogen (NOx) in cigarette smoke (about 1000 ppm) cause oxidation of macromolecules, and deplete antioxidant levels. This is likely to contribute significantly to the pathology of smoking. Smoking is a risk factor for heart disease as well as a wide variety of cancers in addition to lung cancer.
2) Iron (and copper) salts promote the generation of oxidizing radicals from peroxides (Fenton chemistry). Men who absorb significantly more than normal amounts of dietary iron due to a genetic defect (hemochromatosis disease) are at an increased risk for both cancer and heart disease. It has therefore been argued that too much dietary copper or iron, particularly heme iron (which is high in meat), is a risk factor for cardiovascular disease and cancer in normal men
3) Normal diets contain plant food with large amounts of natural phenolic compounds, such as chlorogenic and caffeic acid, that may generate oxidants by redox cycling .
Click here for more about Glutathione and its benefits to our body.
Oxidants, Antioxidants, and the Degenerative Diseases of Aging
Metabolism, like other aspects of life, involves trade-offs. Oxidant by-products of normal metabolism cause extensive damage to DNA, protein, and lipid. We argue that this damage (the same as that produced by radiation) is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune system decline, brain dysfunction and cataracts. Antioxidant defenses against this damage include ascorbate, tocopherol and carotenoids. Fruits and vegetables are the principal source of ascorbate and carotenoids and are one source of tocopherol. Low dietary intake of fruits and vegetables doubles the risk of most types of cancer as compared to high intake and also markedly increases the risk of heart disease and cataracts. Since only 9% of Americans eat the recommended five servings of fruits and vegetables per day the opportunity for improving health by improving diet is great.
The degenerative diseases associated with aging include cancer, cardiovascular disease, immune system decline, brain dysfunction, and cataracts. The functional degeneration of somatic cells during aging appears, in good part, to contribute to these diseases. The relationship between cancer and age in various mammalian species illustrates this point. Cancer increases with about the fifth power of age in both short-lived species, such as rats, and in long-lived species, such as humans.
Thus a marked decrease in age-specific cancer rates has accompanied the marked increase in life span that has occurred in 60 million years of mammalian evolution: i.e., cancer rates are high in a two year old rat, but low in a two year old human. One important factor in longevity appears to be basal metabolic rate, which is about seven times higher in a rat than a human and which could markedly affect the level of endogenous oxidants and other mutagens produced as by-products of metabolism. The level of oxidative DNA damage appears to be roughly related to metabolic rate in a number of mammalian species (cancer/mutation/endogenous DNA adducts/oxygen radicals)
Click here for more about Glutathione and its benefits to our body.
By Bruce N. Ames*, Mark K. Shigenaga, and Tory M. Hagen
The degenerative diseases associated with aging include cancer, cardiovascular disease, immune system decline, brain dysfunction, and cataracts. The functional degeneration of somatic cells during aging appears, in good part, to contribute to these diseases. The relationship between cancer and age in various mammalian species illustrates this point. Cancer increases with about the fifth power of age in both short-lived species, such as rats, and in long-lived species, such as humans.
Thus a marked decrease in age-specific cancer rates has accompanied the marked increase in life span that has occurred in 60 million years of mammalian evolution: i.e., cancer rates are high in a two year old rat, but low in a two year old human. One important factor in longevity appears to be basal metabolic rate, which is about seven times higher in a rat than a human and which could markedly affect the level of endogenous oxidants and other mutagens produced as by-products of metabolism. The level of oxidative DNA damage appears to be roughly related to metabolic rate in a number of mammalian species (cancer/mutation/endogenous DNA adducts/oxygen radicals)
Click here for more about Glutathione and its benefits to our body.
By Bruce N. Ames*, Mark K. Shigenaga, and Tory M. Hagen
Wednesday, February 6, 2008
Inflammation, Free Radicals, and Cytokines
Although acute Inflammation is an important immune system response, chronic inflammation has also been linked to many diseases, including heart disease. Besides the pro-Inflammation cytokines, Inflammation may be related to the overproduction of free radicals (Janeway CA et al 1999).
A free radical is an atom or group of atoms (i.e., a molecule) with unpaired electrons. Free radicals are extremely unstable and react easily with other molecules, thereby changing their chemical composition. Oxygen is especially susceptible to free radical formation. The free radicals derived from oxygen are known as reactive oxygen species, or oxidants.
When the body has increased levels of reactive oxygen species (i.e., when it is experiencing oxidative stress), widespread damage may result. At high concentrations free radicals can damage fats, proteins, and nucleic acids. They can also cause cell death, gene mutations, and cancer ( Moslen MT 1994). Several diseases may be the result of cellular and genetic damage caused by free radicals, including several immune disorders ( Moslen MT 1994).
In order to reduce the damage caused by elevated free radicals and cytokines (which are both part of the natural immune system), the body fights back by producing antioxidants and hormones such as cortisol to suppress the immune system (Grimble RF 1996). Antioxidants are valuable because they pair with unstable free radicals, thereby limiting the damage free radicals can inflict on other cells.
Click here for more about Glutathione and its benefits to our body.
A free radical is an atom or group of atoms (i.e., a molecule) with unpaired electrons. Free radicals are extremely unstable and react easily with other molecules, thereby changing their chemical composition. Oxygen is especially susceptible to free radical formation. The free radicals derived from oxygen are known as reactive oxygen species, or oxidants.
When the body has increased levels of reactive oxygen species (i.e., when it is experiencing oxidative stress), widespread damage may result. At high concentrations free radicals can damage fats, proteins, and nucleic acids. They can also cause cell death, gene mutations, and cancer ( Moslen MT 1994). Several diseases may be the result of cellular and genetic damage caused by free radicals, including several immune disorders ( Moslen MT 1994).
In order to reduce the damage caused by elevated free radicals and cytokines (which are both part of the natural immune system), the body fights back by producing antioxidants and hormones such as cortisol to suppress the immune system (Grimble RF 1996). Antioxidants are valuable because they pair with unstable free radicals, thereby limiting the damage free radicals can inflict on other cells.
Click here for more about Glutathione and its benefits to our body.
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