Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00568 (ascorbate)
 23,072 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peroxidation in isolated, functionally intact rat heart mitochondria was induced by iron/ascorbate or ADP-iron/NAD(P)H. Compared to liver mitochondria, MDA formation was very low and lipohydroperoxides not detected. The NADPH-mediated peroxidation which generally resulted in somewhat higher MDA levels was accompanied by an increasing inhibition of ADP-stimulated respiration. The active respiration was sensitively inhibited at very early stages of MDA formation, whereas in the same period the CAT-insensitive respiration exhibited almost no response at all. It was demonstrated that the decrease in active respiration correlated with the time for half-maximum MDA formation. No considerable degradation of major mitochondrial phospholipids was observed during two hours of incubation. It was not until after complete inhibition of respiration and onset of enhanced MDA formation that cardiolipin, phosphatidylethanolamine and, later, phosphatidylcholine were diminished.
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PMID:Studies of lipid peroxidation in isolated rat heart mitochondria. 273 Jun 31

Gamma-linolenic acid has been shown to suppress the rate of proliferation of a number of malignant cell lines in culture. To test the proposal that this was a specific prostaglandin 1- or 2-series effect, 379 batches of MG63 human osteogenic sarcoma cells were seeded in Greiner flasks and cultured in media supplemented with a range of unsaturated fatty acids and prostaglandins. The monounsaturated fatty acid oleic acid enhanced the rate of cancer cell proliferation. The polyunsaturated fatty acids linoleic acid, gamma-linolenic acid, arachidonic acid, alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, as well as prostaglandins E1 and A1 suppressed the rate of cell proliferation. Total suppression of colony forming and cell proliferation occurred at high levels of polyunsaturated fatty acid supplementation. In addition gamma-linolenic in the form of evening primrose seed oil and vitamin C has been given to 6 patients with histologically diagnosed primary liver cell cancer. Some clinical improvement and reduction in tumor size occurred in 3 cases. One patient has shown remarkable improvement in reduction of liver and tumor size on the CAT scan and reduction of the serum alkaline phosphatase from 2830 to 295 units and gamma-glutamyl transaminase from 274 to 82 units. Thus preliminary clinical results suggest that gamma-linolenic acid may be effective in the management of human cancer patients and further trials should be conducted. However, the cell culture results suggest that although the essential fatty acids suppress proliferation, eicosanoids of all 3 series may be involved. The proliferation suppressive effect of docosahexaenoic acid suggests that other aspects than only eicosanoid activity may also be important in the suppression of cancer cell proliferation.
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PMID:Some effects of the essential fatty acids linoleic acid and alpha-linolenic acid and of their metabolites gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and of prostaglandins A1 and E1 on the proliferation of human osteogenic sarcoma cells in culture. 608 35

We studied the effect of supplementation with vitamins C, E and beta-carotene (PARABION, produced by Syndipharma) on antioxidative status in kidneys of male Wistar rats with diabetes induced by intravenous application of streptozotocin (45 mg.kg-1 of body weight). The animals received subtherapeutic doses of Insulin Interdep (6 U.kg-1 of body weight). A significant decrease of malondialdehyde (MDA), reduced (GSH) and oxidized (GSSG) glutathione and reduction of the activities of Se-glutathione peroxidase (Se-GSH-PX, EC. 1.11.1.9.) and glutathione S-transferase (GST, EC. 2.5.1.18.) were observed in kidneys of diabetic rats treated with these vitamins. On the contrary, the activity of CuZn-superoxide dismutase (CuZn-SOD, EC. 1.15.1.1) and the level of vitamin C (vit. C) increased significantly. No changes were observed for vitamin E (vit. E), beta-carotene and catalase (CAT, EC. 1.11.1.6). Supplementation with vitamins C, E and beta-carotene resulted in an improvement of antioxidative status of kidneys of rats with streptozotocin-induced diabetes.
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PMID:Effect of intake of exogenous vitamins C, E and beta-carotene on the antioxidative status in kidneys of rats with streptozotocin-induced diabetes. 747 41

Age dependence of lipid peroxidation levels estimated as conjugated dienes (CD) of plasma fatty acids was investigated in vegetarian and non-vegetarian males and females aged 11-14, 15-18, 19-39 and 40-60 years. The increase of CD levels with age was found in probands on both types of nutrition up to the age of 40 years. In the first three age groups, lipid peroxidation was insignificantly lower in vegetarians when compared to nonvegetarians. The increase of conjugated dienes was on the level of significance (p < 0.05) in the oldest vegetarians vs nonvegetarians. Therefore, content of defense parameters--antioxidative vitamin and enzyme--was estimated in blood of vegetarians aged 40-60 years. Significantly higher levels of vitamin C and catalase activity were found in vegetarians (C-63.6 and 86.5 mumol/l; CAT-1497 and 1313 U/ml for males and females, respectively) when compared to nonvegetarians (C-41.3 and 54.4 mumol/l; CAT-1192 and 1086 U/ml). A significant negative linear correlation (p < 0.001) for CD-C and CD-CAT was found in both sexes of vegetarians and in nonvegetarian females (p < 0.05 for nonvegetarian males). Important finding is a more pronounced in vegetarians (2.5-3.4 times higher slope of regression lines) indicating positive effect of vegetarian nutrition on efficiency of protection system.
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PMID:Levels of lipid peroxidation and antioxidants in vegetarians. 767 77

In this study, the activities of major enzymes participating in free radical metabolism (xanthine oxidase, XO; Cu,Zn and Mn superoxide dismutases, SOD; glutathione peroxidase, GSH-Px; catalase, CAT) were measured in kidney tissues from guinea pigs treated with gentamicin alone (200 mg/kg/day), gentamicin plus vitamin C (600 mg/kg/day), gentamicin plus vitamin E (400 mg/kg/day), and gentamicin plus vitamins C and E together for 10 days, and from animals treated with physiological saline solution alone during this period. We found no significant differences between control and gentamicin groups with respect to XO and Cu,Zn-SOD activities. However, the activities of Mn-SOD, GSH-Px, and CAT were found to be significantly depressed in the gentamicin-treated group relative to controls. In the gentamicin plus vitamin C group, the renal tissue Mn-SOD activity was found to be higher as compared with control and gentamicin groups. In this group, XO, GSH-Px and CAT activities were also higher than in the gentamicin-treated group, but no statistically significant differences existed between the values of this group and controls. Similar results were also observed in the gentamicin plus vitamin E group for Mn-SOD, GSH-Px, CAT, and XO. In this group, the Cu,Zn-SOD activity was found to be decreased as compared with control and gentamicin groups. In the gentamicin plus vitamins C and E group, the Cu,Zn-SOD activity was found to be decreased, the XO activity to be unchanged, and Mn-SOD, GSH-Px, and CAT activities to be increased as compared with the gentamicin and control groups. The results suggest that the enzymatic antioxidant defense system was significantly disturbed because of the suppressed activities of Mn-SOD, GSH-Px, and CAT in the kidney tissues from animals treated with gentamicin. However, vitamins C and E given concurrently with gentamicin completely abrogated this enzymatic suppression.
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PMID:Reduced enzymatic antioxidant defense mechanism in kidney tissues from gentamicin-treated guinea pigs: effects of vitamins E and C. 868 38

The defenses against the production of free radicals and reactive oxygen species (ROS) are to be found in plasma (ascorbate, urate, alpha tocopherol) and in erythrocytes (superoxide dismutase or SOD; catalase or CAT; glutathione peroxidase or GPx). In chronic renal failure, an increased lipid peroxidation and a reduced antioxidant activity seem to be present, but previous reports are conflicting. To clarify the peroxidative status and the defense mechanisms taking place in patients on dialysis, in 30 patients on dialysis (15 men, 15 women) and in 20 control subjects (10 men, 10 women), the following parameters were measured: plasma 4-hydroxinonenal (4-HNE) and erythrocyte reduced glutathione (GSH), SOD, GPx, and glucose-6-phosphate dehydrogenase (G-6-PD). Patients on dialysis, in comparison with control subjects, had 1) increased levels of 4-HNE (p < 0.001); 2) a significant increase in erythrocyte-GSH (p < 0.05); and 3) significant decreases in erythrocyte-SOD (p < 0.001), erythrocyte-G-6-PD (p < 0.005), and the erythrocyte-SOD/GPx ratio (p < 0.001). The dialysis procedure induced a certain reduction in plasma 4-HNE, an increase in erythrocyte-SOD activity, and an important consumption of erythrocyte-GSH, while the erythrocyte-SOD/GPx ratio changed. The current study supports the view that 1) erythrocytes act as small detoxifying packets; 2) in chronic renal failure, the antioxidant system is largely inadequate; and 3) in patients on dialysis, the antioxidant mechanism of erythrocytes in scavenging ROS is effectively exerted during dialysis but remains largely inadequate, as signs of lipid peroxidation persist with time.
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PMID:The role of erythrocytes in the deperoxidative processes in people on hemodialysis. 894 13

MeAN administration (40mg/kg body wt/day (i.e. 1/5 of LD50) resulted in increased levels of lipid peroxidation products, conjugated dienes and lipofuscin-like substances in rat liver. Significant decrease in GSH and a decreased activity of hepatic SOD, CAT and GPx were observed. There was also an increase in glutathione S-transferase and G6PD activities, decreased plasma ceruloplasmin and vitamin C implying oxidative stress caused by MeAN.
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PMID:Methacrylonitrile induced oxidative stress in rat liver. 959 37

It has been suggested that antioxidants play a role in regulating or modulating senescence dynamics of plant tissues. Ethylene has been shown to promote early plant senescence while controlled atmospheres (CA; reduced O2 levels and elevated CO2 levels) can delay its onset and/or severity. In order to examine the possible importance of various antioxidants in the regulation of senescence, detached spinach (Spinacia oleracea L.) leaves were stored for 35 d at 10 degrees C in one of three different atmospheres: (1) ambient air (0.3% CO2, 21.5% O2, 78.5% N2), (2) ambient air + 10 ppm ethylene to promote senescence, or (3) CA (10% CO2, 0.8% O2 and 89.2% N2) to delay senescence. At weekly intervals, material was assessed for activities of the antioxidant enzymes ascorbate peroxidase (ASPX; EC 1.11.1.11), catalase (CAT; EC 1.11.1.6), dehydroascorbate reductase (DHAR; EC 1.8.5.4), glutathione reductase (GR; EC 1.6.4.2), monodehydroascorbate reductase (MDHAR; EC 1.6.5.4), and superoxide dismutase (SOD; EC 1.15.1.1), and concentrations of the water-soluble antioxidant compounds ascorbate and glutathione. Indicators of the rate and severity of senescence (lipid peroxidation, chlorophyll, and soluble protein levels) were also determined. Results indicated that the rate and severity of senescence was similar between the leaves stored in ambient air or CA until day 35, at which point the ambient air-stored leaves exhibited a sharp increase in lipid peroxidation. Tissues under both storage regimes demonstrated significant declines only in levels of ASPX, CAT, and ascorbate. Glutathione content in the CA-stored tissue also significantly dropped, but only on day 35. In contrast, spinach leaves stored in ambient air + ethylene experienced a rapid decrease in levels of all the antioxidants assessed except SOD. Declines in levels of ASPX, CAT, and ascorbate over the 35 d storage period regardless of the composition of the storage atmosphere suggests that regulation of H2O2 levels plays an important role in both the dynamics and severity of post-harvest senescence of spinach.
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PMID:The effects of ethylene, depressed oxygen and elevated carbon dioxide on antioxidant profiles of senescing spinach leaves. 1093 20

The effect of diets containing antioxidant vitamins and trace elements on chicken tissue activities of SOD, CAT, GSH-Px and of LPO levels was investigated. Chickens, 45 weeks of age were divided into six groups: control group, Cu group (13.2 mg Cu kg(-1) diet); Se group (0.07 mg Se kg(-l) diet); vitamin E group (70 mg DL-alpha-tocopherol acetate kg(-1) diet) and a constant level vitamin C, 200 mg kg(-1) diet); vitamin A group (240 mg retinol acetate kg(-1) diet) and vitamin C group (500 mg ascorbic acid kg(-1) diet). Significant variation of these antioxidant enzyme activities and LPO levels according to gender was demonstrated statistically. In the Cu group, CuZnSOD activity in the liver, erythrocyte, kidney and heart significantly increased by 75, 40, 12, 12% respectively (P<0.05). MnSOD activity in the heart, liver, kidney and brain of the vitamin C and in the heart of Cu group were found to be increased by approximately 15%, while in liver tissue of the Cu group it was reduced by 19% (P<0.05). GSH-Px activities in the Se, vitamin E and C groups were significantly increased, conversely LPO levels decreased (P<0.001). CAT activities in the liver and heart of the vitamin C group were significantly decreased (by 32%), but in kidney tissue only that of the Cu group was increased from 30.2 +/- 4.767 to 144.49 +/- 6.93 U mg(-1) P<0.001. The resistance to stress of the vitamin E and C groups, which had significantly increased activities of antioxidant enzymes and decreased lipid peroxide levels, were determined in 60% moisture medium at 45 degrees C.
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PMID:The effects of some antioxidant vitamin- and trace element-supplemented diets on activities of SOD, CAT, GSH-Px and LPO levels in chicken tissues. 1133 37

The response of the antioxidant system to salt stress was studied in the roots of the cultivated tomato Lycopersicon esculentum Mill. cv. M82 (Lem) and its wild salt-tolerant relative L. pennellii (Corr.) D'Arcy accession Atico (Lpa). Roots of control and salt (100 mM NaCl)-stressed plants were sampled at various times after commencement of salinization. A gradual increase in the membrane lipid peroxidation in salt-stressed root of Lem was accompanied with decreased activities of the antioxidant enzymes: superoxide dismutase (SOD; EC 1.15.1.1), catalase (CAT; EC 1.11.1.6), ascorbate peroxidase (APX; EC 1.11.1.11) and decreased contents of the antioxidants ascorbate and glutathione and their redox states. In contrast, increased activities of the SOD, CAT, APX, monodehydroascorbate reductase (MDHAR; EC 1.6.5.4), and increased contents of the reduced forms of ascorbate and glutathione and their redox states were found in salt-stressed roots of Lpa, in which the level of membrane lipid peroxidation remained unchanged. It seems that the better protection of Lpa roots from salt-induced oxidative damage results, at least partially, from the increased activity of their antioxidative system.
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PMID:Response of the cultivated tomato and its wild salt-tolerant relative Lycopersicon pennellii to salt-dependent oxidative stress: The root antioxidative system. 1147 8


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