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.
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Showing posts with label oxidative stress. Show all posts
Showing posts with label oxidative stress. Show all posts
Monday, February 11, 2008
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.
Sunday, February 3, 2008
Cause of Parkinson Disease
Although Parkinson’s disease can occur from viral infections or exposure to environmental toxins, such as pesticides (gardeners and farmers are more prone to Parkinson's disease).
The causes of the majority of cases are not well known. Scientists suspect that oxidative damage to neurons in the substantia nigra could well be one of the major causes, particularly due to the depletion of the antioxidants glutathione.
People who sustain substantial head injuries face an increased risk of developing Parkinson’s disease years later.
The cause of Parkinson's disease is unknown.
Many researchers believe that several factors combined are involved: free radicals, accelerated aging, environmental toxins, and genetic predisposition.
It may be that free radicals—unstable and potentially damaging molecules that lack on electron—are involved in the degeneration of dopamine-producing cells.
Free radicals add an electron by reacting with nearby molecules in a process called oxidation, which can damage nerve cells.
Chemicals called antioxidants normally protect cells from oxidative stress and damage. If antioxidative action fails to protect dopamine-producing nerve cells, they could be damaged and, subsequently, Parkinson’s disease could develop.
Dysfunctional antioxidative mechanisms are associated with older age as well, suggesting that the acceleration of age-related changes in dopamine production may be a factor.
Exposure to an environmental toxin, such as a pesticide, that inhibits dopamine production and produces free radicals and oxidation damage may be involved.
The causes of the majority of cases are not well known. Scientists suspect that oxidative damage to neurons in the substantia nigra could well be one of the major causes, particularly due to the depletion of the antioxidants glutathione.
People who sustain substantial head injuries face an increased risk of developing Parkinson’s disease years later.
The cause of Parkinson's disease is unknown.
Many researchers believe that several factors combined are involved: free radicals, accelerated aging, environmental toxins, and genetic predisposition.
It may be that free radicals—unstable and potentially damaging molecules that lack on electron—are involved in the degeneration of dopamine-producing cells.
Free radicals add an electron by reacting with nearby molecules in a process called oxidation, which can damage nerve cells.
Chemicals called antioxidants normally protect cells from oxidative stress and damage. If antioxidative action fails to protect dopamine-producing nerve cells, they could be damaged and, subsequently, Parkinson’s disease could develop.
Dysfunctional antioxidative mechanisms are associated with older age as well, suggesting that the acceleration of age-related changes in dopamine production may be a factor.
Exposure to an environmental toxin, such as a pesticide, that inhibits dopamine production and produces free radicals and oxidation damage may be involved.
Thursday, January 17, 2008
Chronic Alcoholism Alters Systemic and Pulmonary Glutathione Redox Status
Rationale: Previous studies have linked the development and severity of acute respiratory distress syndrome with a history of alcohol abuse. In clinical studies, this association has been centered on depletion of pulmonary Glutathione and subsequent chronic oxidant stress.
Objectives: The impact on redox potential of the plasma or pulmonary pools, however, has never been reported.
Methods: Plasma and bronchoalveolar lavage fluid were collected from otherwise healthy alcohol-dependent subjects and control subjects matched by age, sex, and smoking history.
Measurements and Main Results: Redox potential was calculated from measured reduced and oxidized Glutathione in plasma and lavage. Among subjects who did and did not smoke, lavage fluid Glutathione redox potential was more oxidized in alcohol abusers by approximately 40 mV, which was not altered by dilution. This oxidation of the airway lining fluid associated with chronic alcohol abuse was independent of smoking history. A shift by 20 mV in plasma Glutathione redox potential, however, was noted only in subjects who both abused alcohol and smoked.
Conclusions: Chronic alcoholism was associated with alveolar oxidation and, with smoking, systemic oxidation. However, systemic oxidation did not accurately reflect the dramatic alcohol-induced oxidant stress in the alveolar space.
Although there was compensation for the oxidant stress caused by smoking in control groups, the capacity to maintain a reduced environment in the alveolar space was overwhelmed in those who abused alcohol. The significant alcohol-induced chronic oxidant stress in the alveolar space and the subsequent ramifications may be an important modulator of the increased incidence and severity of acute respiratory distress syndrome in this vulnerable population.
Mary Y. Yeh1, Ellen L. Burnham2, Marc Moss2 and Lou Ann S. Brown1
Objectives: The impact on redox potential of the plasma or pulmonary pools, however, has never been reported.
Methods: Plasma and bronchoalveolar lavage fluid were collected from otherwise healthy alcohol-dependent subjects and control subjects matched by age, sex, and smoking history.
Measurements and Main Results: Redox potential was calculated from measured reduced and oxidized Glutathione in plasma and lavage. Among subjects who did and did not smoke, lavage fluid Glutathione redox potential was more oxidized in alcohol abusers by approximately 40 mV, which was not altered by dilution. This oxidation of the airway lining fluid associated with chronic alcohol abuse was independent of smoking history. A shift by 20 mV in plasma Glutathione redox potential, however, was noted only in subjects who both abused alcohol and smoked.
Conclusions: Chronic alcoholism was associated with alveolar oxidation and, with smoking, systemic oxidation. However, systemic oxidation did not accurately reflect the dramatic alcohol-induced oxidant stress in the alveolar space.
Although there was compensation for the oxidant stress caused by smoking in control groups, the capacity to maintain a reduced environment in the alveolar space was overwhelmed in those who abused alcohol. The significant alcohol-induced chronic oxidant stress in the alveolar space and the subsequent ramifications may be an important modulator of the increased incidence and severity of acute respiratory distress syndrome in this vulnerable population.
Mary Y. Yeh1, Ellen L. Burnham2, Marc Moss2 and Lou Ann S. Brown1
Tuesday, January 15, 2008
Glutathione in cancer biology and therapy
The Glutathione (GSH ) content of cancer cells is particularly relevant in regulating mutagenic mechanisms, DNA synthesis, growth, and multidrug and radiation resistance.
In malignant tumors, as compared with normal tissues, that resistance associates in most cases with higher GSH levels within these cancer cells. Thus, approaches to cancer treatment based on modulation of GSH should control possible growth-associated changes in GSH content and synthesis in these cells. Despite the potential benefits for cancer therapy of a selective GSH-depleting strategy, such a methodology has remained elusive up to now.
Metastatic spread, not primary tumor burden, is the leading cause of cancer death. For patient prognosis to improve, new systemic therapies capable of effectively inhibiting the outgrowth of seeded tumor cells are needed.
Interaction of metastatic cells with the vascular endothelium activates local release of proinflammatory cytokines, which act as signals promoting cancer cell adhesion, extravasation, and proliferation.
Recent work shows that a high percentage of metastatic cells with high GSH levels survive the combined nitrosative and oxidative stresses elicited by the vascular endothelium and possibly by macrophages and granulocytes. ?-Glutamyl transpeptidase overexpression and an inter-organ flow of GSH (where the liver plays a central role), by increasing cysteine availability for tumor GSH synthesis, function in combination as a metastatic-growth promoting mechanism.
The present review focuses on an analysis of links among GSH, adaptive responses to stress, molecular mechanisms of invasive cancer cell survival and death, and sensitization of metastatic cells to therapy. Experimental evidence shows that acceleration of GSH efflux facilitates selective GSH depletion in metastatic cells.
Estrela JM; Ortega A; Obrador EDepartment of Physiology, University of Valencia, Valencia, Spain.
Click here for more about Glutathione and its benefits to our body.
Why is Glutathione Essential to Health?
Glutathione's three major roles in the body are summarized by the letters A-B-C.
- Anti-oxidant- Blood Booster- Cell Detoxifier
In malignant tumors, as compared with normal tissues, that resistance associates in most cases with higher GSH levels within these cancer cells. Thus, approaches to cancer treatment based on modulation of GSH should control possible growth-associated changes in GSH content and synthesis in these cells. Despite the potential benefits for cancer therapy of a selective GSH-depleting strategy, such a methodology has remained elusive up to now.
Metastatic spread, not primary tumor burden, is the leading cause of cancer death. For patient prognosis to improve, new systemic therapies capable of effectively inhibiting the outgrowth of seeded tumor cells are needed.
Interaction of metastatic cells with the vascular endothelium activates local release of proinflammatory cytokines, which act as signals promoting cancer cell adhesion, extravasation, and proliferation.
Recent work shows that a high percentage of metastatic cells with high GSH levels survive the combined nitrosative and oxidative stresses elicited by the vascular endothelium and possibly by macrophages and granulocytes. ?-Glutamyl transpeptidase overexpression and an inter-organ flow of GSH (where the liver plays a central role), by increasing cysteine availability for tumor GSH synthesis, function in combination as a metastatic-growth promoting mechanism.
The present review focuses on an analysis of links among GSH, adaptive responses to stress, molecular mechanisms of invasive cancer cell survival and death, and sensitization of metastatic cells to therapy. Experimental evidence shows that acceleration of GSH efflux facilitates selective GSH depletion in metastatic cells.
Estrela JM; Ortega A; Obrador EDepartment of Physiology, University of Valencia, Valencia, Spain.
Click here for more about Glutathione and its benefits to our body.
Why is Glutathione Essential to Health?
Glutathione's three major roles in the body are summarized by the letters A-B-C.
- Anti-oxidant- Blood Booster- Cell Detoxifier
Glutathione, oxidative stress and aging
The theory of aging proposes that the impairment in physiological performance associated with aging is caused by the detrimental effects of oxygen free radicals. This is interesting because it provides us with a theoretical framework to understand aging and because it suggests a rationale for intervention, i.e., antioxidant administration. Thus, the study of antioxidant systems of the cell may be very important in gerontological studies. Glutathione is one of the main nonprotein antioxidant in the cell which, together with its related enzymes, constitute the “Glutathione system.” The involvement of Glutathione in aging has been known since the early seventies. Several studies have reported that reduced Glutathione is decreased in cells from old animals, whereas oxidized Glutathione tends to be increased. Recent experiments from our laboratory have underscored the importance of cellular compartmentation of Glutathione. MitochondrialGlutathione plays a key role in the protection against free radical damage associated with aging. Oxidative damage to mitochondrial DNA is directly related to an oxidation of mitochondrialGlutathione. In fact, aging is associated with oxidative damage to proteins, nucleic acids, and lipids. These molecular lesions may be responsible for the low physiological performance of aged cells. Thus, antioxidant supplementation may be a rational way to partially protect against age-associated impairment in performance. Apoptosis, a programmed cell death, is an area of research which has seen an explosive growth. Glutathione is involved in apoptosis: apoptotic cells have lower levels of reduced Glutathione, and administration of Glutathione precursors prevent, or at least delay, apoptosis. Age-associated diseases constitute a major concern for researchers involved in aging. Free radicals are involved in many such diseases; for instance, cancer, diabetes or atherosclerosis. The key role of Glutathione and other antioxidant in the pathophysiology of aging and age-associated diseases is discussed in this review.
Juan Sastre1, Federico V. Pallardó1 and Jose Viña Department of Physiology, Faculty of Medicine, University of Valencia, Spain Dept. Fisiologia, Facultad de Medicina, Avenida Blasco Ibanez 17, 46010 Valencia, Spain
Juan Sastre1, Federico V. Pallardó1 and Jose Viña Department of Physiology, Faculty of Medicine, University of Valencia, Spain Dept. Fisiologia, Facultad de Medicina, Avenida Blasco Ibanez 17, 46010 Valencia, Spain
Wednesday, January 9, 2008
Why is Glutathione important for Sperm Quality and Fertility?
A decrease in levels of reduced glutathione (GSH) during sperm production is known to disrupt the membrane integrity of spermatozoa due to increased oxidative stress.
Intracellular glutathione levels of spermatozoa are known to be decreased in certain populations of infertile men. Compared with a control group, the infertile men in all groups had significantly higher levels of ROS and lower levels of total antioxidants. There is strong clinical evidence to show that men diagnosed with infertility have high levels of oxidative stress that may impair the quality of their sperm.
In some groups, higher levels of ROS were associated with lower sperm counts and defective sperm structure, while lower antioxidant levels correlated with reduced sperm movement.Previous evidence has also shown that oxidative stress can decrease a sperm's life span, its motility, and its ability to penetrate the oocyst, or egg cell.
Up to 40% of men with unexplained male infertility have higher levels of free radical activity in their bodies. Because men with high levels of ROS have a seven-fold lower likelihood of inducing a pregnancy than men with lower levels, researchers recommend that treatment for infertile men should include strategies to reduce oxidative stress and improve sperm quality.
By Priya F. Shah
Intracellular glutathione levels of spermatozoa are known to be decreased in certain populations of infertile men. Compared with a control group, the infertile men in all groups had significantly higher levels of ROS and lower levels of total antioxidants. There is strong clinical evidence to show that men diagnosed with infertility have high levels of oxidative stress that may impair the quality of their sperm.
In some groups, higher levels of ROS were associated with lower sperm counts and defective sperm structure, while lower antioxidant levels correlated with reduced sperm movement.Previous evidence has also shown that oxidative stress can decrease a sperm's life span, its motility, and its ability to penetrate the oocyst, or egg cell.
Up to 40% of men with unexplained male infertility have higher levels of free radical activity in their bodies. Because men with high levels of ROS have a seven-fold lower likelihood of inducing a pregnancy than men with lower levels, researchers recommend that treatment for infertile men should include strategies to reduce oxidative stress and improve sperm quality.
By Priya F. Shah
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