Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of the antioxidant enzymes catalase (CAT), peroxidases (POD), and superoxide dismutases (SOD) in whole blood and different blood fractions was analyzed in 20 normal human beings and correlated with the chromosomal sensitivity of lymphocytes to bleomycin (BLM) (measured as frequency of dicentric chromosomes per BLM dose). Our results demonstrate that both the physiologic activities of the enzymes and the chromosomal sensitivity to BLM exhibit an ample and significant interindividual variability. An inverse and linear correlation between chromosomal sensitivity to BLM and the concentration of 1) CAT and POD in plasma and 2) SOD in whole blood, erythrocytes, and plasma was found. On the other hand, the chromosomal sensitivity to BLM showed a direct correlation with the concentration of SOD and POD in mononuclear leukocytes. It is suggested that a determination of antioxidant enzyme (AOE) activities in a given cell population may serve to predict the chromosomal sensitivity to BLM.
Cancer Genet Cytogenet 1992 Dec
PMID:Chromosomal sensitivity of human lymphocytes to bleomycin. Influence of antioxidant enzyme activities in whole blood and different blood fractions. 128 12

Dose intensity is emerging as a crucial determinant of success in cytotoxic cancer therapy; however, myelosuppression presents as one of the major complications encountered with increased dose intensity. Therefore, investigators are looking at the use of cytokine administration in combination with cytotoxic therapy to overcome this problem. Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) have been shown to be beneficial in protecting the hematopoietic system from radiation and chemotherapy. In this report, we give an overview of studies using IL-1 and TNF-alpha as protective agents and discuss possible mechanisms involved in their protective action. Mice pretreated with IL-1 and/or TNF-alpha were shown to be protected from the lethal effects of radiation and it has been suggested that the mechanism for this protection may be through the production of the antioxidant enzyme manganese superoxide dismutase. Similarly, aldehyde dehydrogenase, an enzyme important in the metabolic pathway of cyclophosphamide compounds, has been implicated as being important in the protection of hematopoietic cells from 4-hydroperoxycyclophosphamide. While IL-1 and TNF-alpha stimulate both of these enzymes, other mechanisms are probably also operative for other forms of chemotherapy, i.e. IL-1 and TNF-alpha were shown to protect hematopoietic progenitors from phenylketophosphamide, a cyclophosphamide derivative that is not metabolized by the enzyme aldehyde dehydrogenase. Furthermore, malignant as well as normal cells may possess receptors for these cytokines; therefore, IL-1 and TNF-alpha will have to be selective in their protection. They must be capable of protecting normal hematopoietic cells while rendering malignant cells susceptible to the toxic actions of the chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The therapeutic potential of interleukin-1 and tumor necrosis factor on hematopoietic stem cells. 129 Sep 56

Although the effects of cigarette smoking on a variety of diseases, from cancer through emphysema and cardiovascular illness are well documented, direct effects on the levels of macro- and micronutrients in the body are reported less frequently. In fact, imbalances in these nutrients may have a role in many of the pathological conditions attributed to smoking. Tobacco smoke contains numerous compounds emitted as gases and condensed tar particles, many of them being oxidants and prooxidants, capable of producing free radicals thus enhancing lipid peroxidation in biological membranes. Vitamin E, vitamin C, B-carotene and selenium are involved in the overall cellular anti-oxidant defense against deleterious effects of reactive oxygen species. Smoking has been shown to lower the level of vitamin C and B-carotene in plasma. Cadmium, naturally found in tobacco, decreases the bioavailability of selenium and acts antagonistically to zinc, a cofactor for the antioxidant enzyme, superoxide dismutase. Vitamin E, the principle lipid-soluble antioxidant, may be at suboptimal levels in tissues of smokers. In addition, tobacco constituents have been shown to reduce levels of several vitamins of the B-complex. Nutritional status in smokers may be further compromised by an inadequate diet. Data from the Second National Health and Nutrition Examination Survey indicates that smokers are less likely to consume fruits and vegetables, particularly those high in vitamin C and carotenes. Cessation of smoking is the obvious solution to ending cigarette-related problems. In the world as it is, however, the medical community should be responsible for making recommendations to lower the risk in smokers to tobacco related diseases. Nutritionists could have a role in this process. There exists a lively debate as to where levels of nutrients should be set. Additional vitamin C has already been recommended for smokers. Should other antioxidants also be increased? Arguments for the against are considered.
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PMID:Cigarette smoking-nutritional implications. 178 36

Antioxidant micronutrients are one of the body's primary defenses against free radicals and reactive oxygen molecules. Carotenoids, vitamin C, and vitamin E trap these molecules, and selenium is an essential component of an antioxidant enzyme. There is considerable support from animal studies for a protective effect of antioxidant micronutrients on cancer. However, the role of these micronutrients in cancer prevention in humans is less clear. Diet studies suggest protective effects of fruits and vegetables on risk of cancer at several sites. Inverse associations between dietary carotenoids and serum beta-carotene and lung cancer have been observed repeatedly. Vitamin C has also been consistently inversely associated with risk of oral and esophageal cancer in diet studies and with stomach cancer in both diet and plasma studies. It remains unknown, however, whether carotenoids and vitamin C or some other component of fruits and vegetables, the primary sources of these micronutrients, prevent cancer in humans. Selenium has been inversely correlated with cancers at numerous sites in ecologic studies, but observational studies do not provide strong support for a protective effect of selenium on cancer at any site. There also is not strong support for a protective effect of vitamin E on cancer in humans. Results of studies on the association of antioxidant micronutrients with cancer at many sites are inconsistent. This could be due to lack of a true protective effect or could be related to methodologic problems in assessing dietary intake in epidemiologic studies.
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PMID:Antioxidant micronutrients in cancer prevention. 202 68

Relative cell survival and activity of the free radical scavenging enzymes superoxide dismutase, catalase, and glutathione peroxidase were measured in cloned normal (MEA) and SV40-transformed (SVMEA) mouse embryo cells exposed at 44 degrees C for 0-3 h. At 37 degrees C, all three enzymes were 2-5 times higher in MEA than in SVMEA. Hyperthermia did not significantly alter enzyme levels in either cell line but selectively reduced transformed cell survival to less than 5% while relative survival of normal cells remained above 75%. The latter, however, could be reduced to 25% when normal cells were pretreated with 3 mM diethyldithiocarbamate, an inhibitor of copper- and zinc-containing superoxide dismutase. Similar treatment rendered SVMEA extremely thermosensitive. On the other hand, sublethal heat treatment (15 min at 45 degrees C) of cultured cells resulted in a relative thermal resistance upon subsequent exposure to 45 degrees C for 1-4 h. This induced thermotolerance was associated with a rise in antioxidant enzyme levels and both became significant only 4-6 h after the initial heat treatment. Induced enzyme and thermotolerance levels in transformed cells remained, nonetheless, far below those of normal cells. The data show that inherent (in MEA) as well as induced (in SVMEA) thermotolerance is associated with high antioxidant enzyme levels while the reverse is true in the case of inherent (in SVMEA) and induced (in MEA) thermosensitivity. These findings suggest that increased production of oxygen free radicals may be involved in hyperthermic cell injury, which then becomes a function of basal or inducible levels of antioxidant enzymes. Induction of the latter by hyperthermia is apparently inefficient in transformed cells making them more vulnerable. Enzyme induction seems also to require a lag period of 4-6 h suggesting the possible involvement of an intermediate inducer(s) at molecular level. The so-called heat shock proteins may be candidates for such a role.
Cancer Res 1987 Jul 01
PMID:Antioxidant enzymes and survival of normal and simian virus 40-transformed mouse embryo cells after hyperthermia. 303 17

Increasing evidence suggests a role for reactive free radical oxygen species in the multi-stage events of chemical carcinogenesis. We hypothesized that variations in the level of superoxide dismutase (SOD), a major endogenous antioxidant enzyme, may account in part for variations in susceptibility to cancer induced by polycyclic aromatic hydrocarbons (PAH). The SOD activity of mammary epithelial cells from rats with varying susceptibility to dimethylbenz[a]anthracene (DMBA)-induced breast cancer was assayed. Ageing, pregnancy and previous multiple pregnancies reduce susceptibility of Sprague--Dawley female rats to DMBA. These decreases in susceptibility were correlated with increased levels of SOD activity. Only minor differences in SOD activity was observed in mammary epithelium of genetic strains of rats with differences in susceptibility to DMBA. These data suggest that, in models where physiological differences may account for variations in effectiveness of PAH to induce mammary cancer, SOD activity is inversely correlated with breast cancer susceptibility and support the hypothesis that cancer susceptibility may be partially mediated through reactive free radical oxygen intermediates.
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PMID:Relationships between cellular superoxide dismutase and susceptibility to chemically induced cancer in the rat mammary gland. 308 49

Selenium ingestion may inhibit carcinogenesis. Epidemiologic studies have shown that age-adjusted death rates for cancer at most head and neck sites are lower in states where the soil and forage crops contain higher levels of selenium. The mode of action is incompletely understood, but may be mediated through an increase in the activity of the selenium dependent, antioxidant enzyme glutathione peroxidase (GSH-Px). The authors studied blood selenium levels and blood and tissue GSH-Px activities in 50 patients with untreated cancer of the oral cavity and oropharynx. Mean erythrocyte selenium and glutathione peroxidase were significantly depressed when compared to age-matched controls. Mean plasma selenium, on the other hand, was significantly elevated in the cancer patient group. Data from subsets within the cancer patient group were also discussed. GSH-Px activity did not differ in tumor and adjacent normal tissue. The concept of chemoprevention of carcinogenesis with inhibitory chemical compounds is particularly apropos to head and neck cancer control. Further work is indicated to determine if ingestion of supplemental selenium corrects the abnormalities identified here, and what affect, if any, this would have on the development and behavior of squamous cell cancers in the upper aerodigestive tract.
Cancer 1983 Jan 01
PMID:Selenium and glutathione peroxidase levels in patients with epidermoid carcinoma of the oral cavity and oropharynx. 682 99

Reactive oxygen species are generated physiologically in cells with a significant increase in certain pathological conditions, such as inflammation, cancer, aging, degenerative disease. If endogenous antioxidant systems, in our study represented by glutathione peroxidase, are exceeded by this oxidant flux, tissue injury may occur. Activity of glutathione peroxidase (GPx) was determined using Beutler's modified spectrophotometric assay in erythrocytes from autosomal dominant polycystic kidney disease patients. Activity of glutathione peroxidase was significantly (at p < 0.0001) lower there (17.75 +/- 3.69 U/g haemoglobin) compared to the control group (23.26 +/- .61 U/g Hb). Lower antioxidant enzyme defence system of ADPKD patients, here represented by GPx, can potentiate injury caused by free radicals and possibly play a role in the progression of autosomal dominant polycystic kidney disease.
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PMID:Activity of the antioxidant enzyme, glutathione peroxidase, on autosomal dominant polycystic kidney disease patients. 762 19

In summary, it is well established that moderate calorie restriction or reduction in overall high calorie food intake prevents or forestalls the development of age-associated disease incidence such as breast cancer and renal disease in rodents. A similar approach could also readily be applied in humans for preventing the risk and rise of life-shortening diseases. Many age-associated diseases, particularly autoimmune diseases with viral etiology, appear to be exacerbated in the presence of adverse lipid intake such as an increased level of vegetable oils or trans-fatty acids from the usage of hydrogenated dietary oils. At present, nearly 35-40% of the total calories are from dietary fats and/or of lipid origin. Although usage of saturated fat, which increases cardiovascular disease, has been reduced to a large extent in the United States, consumption of both monounsaturated and polyunsaturated fats of omega-6 origin has either increased or simply been substituted in place of saturated fats. Further, for the past 50 years, a significant reduction in highly polyunsaturated fat consumption such as marine oil has also occurred specifically in the United States. The reduction in omega-3 lipids of marine or vegetable source occurs primarily because of short shelf life due to rancidity. However, the increased consumption of omega-6 or a vegetable source of oils and decreased omega-3 intake may increase in vivo the production of free radicals and higher proinflammatory cytokines. Our ongoing studies reveal that proinflammatory vegetable oil could increase autoimmune disease by increasing the free radical formation by decreasing the antioxidant enzyme mRNA levels, thereby further decreasing immune function, particularly the production of anti-inflammatory cytokines such as IL-2 and TGF beta mRNA levels. In contrast, omega-3 lipid intake in the presence of an antioxidant supplement appears to exert protection against autoimmunity by enhancing antioxidant enzymes and TGF beta mRNA levels and by preventing the rise in oncogene expression. However, detailed studies are required to establish the protective and deleterious role of different commonly consumed lipids or dietary oils by the general population, particularly during middle and aging years. Further, we also propose that combining nonsteroidal drug therapy along with moderate calorie reduction in the presence of more protective omega-3 dietary lipids of either marine or vegetable source and decreasing the levels of mono- and polyunsaturated lipids may provide additional protection against the age-associated rise in malignancy and autoimmune disorders.
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PMID:Dietary lipids and risk of autoimmune disease. 805 Jan 92

The effects various drugs exert on antioxidant enzyme and glyoxalase activity in rat livers were studied. All drugs tested provoked a marked reduction in glutathione peroxidase and a small drop in both glyoxalase I and II activity. It is hypothesized that the substances tested support tumour development by neutralizing organic peroxides, thereby favouring the oxidation of carcinogens and, as a consequence, the formation of metabolites that trigger neoplastic transformation. The reduction in glyoxalase activity is probably attributable to the enhanced cell proliferation induced by the treatment.
Bull Cancer 1993 Jan
PMID:Putative role of antioxidant enzymes and glyoxalases in carcinogenesis. 820 20


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