PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “GLUTATHIONE REDUCTASE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 991 records · Page 55Linked to original sources
PubMed2004

Influence of treatment of diabetic rats with combinations of pycnogenol, beta-carotene, and alpha-lipoic acid on parameters of oxidative stress.

Treatment with antioxidants may act more effectively to alter markers of free radical damage in combinations than singly. This study has determined whether treatment with combinations of pycnogenol, beta-carotene, and alpha-lipoic acid was more effective at reducing oxidative stress in diabetic rats than treatment with these antioxidants alone. It is not feasible, based on this study, to assume that there are interactive effects that make combinations of these antioxidants more effective than any one alone to combat oxidative stress. Female Sprague-Dawley rats, normal and streptozotocin-induced diabetic, were treated (10 mg/kg/day ip for 14 days) with pycnogenol, beta-carotene, pycnogenol + beta-carotene, or pycnogenol + beta-carotene + alpha-lipoic acid; controls were untreated. Concentrations of thiobarbituric acid reactive substances, glutathione and glutathione disulfide, and activities of glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase were measured in liver, kidney, and heart. Four types of effects were observed: (1) treatment with beta-carotene alone either reversed (cardiac glutathione disulfide) or elevated (cardiac glutathione, hepatic glutathione peroxidase activity) levels seen in diabetic animals; (2) beta-carotene alone produced no effect, but pycnogenol both alone and in combinations elevated (renal glutathione peroxidase and glutathione reductase activities, hepatic glutathione reductase activity and glutathione disulfide) or depressed (cardiac glutathione disulfide) levels seen in untreated diabetic animals; (3) all treatments with antioxidants, either alone or in combination, either normalized (lipid peroxidation in all tissues), elevated (hepatic GSH, cardiac glutathione peroxidase activity), or had no effect on (activities of hepatic catalase and superoxide dismutase in all tissues) levels seen in diabetic animals; (4) in only one case (cardiac glutathione reductase activity) levels in diabetic animals treated with combinations of antioxidants were normal, but elevated in animals treated with either antioxidant alone. Antioxidant effects seem to be dependent on the nature of the antioxidant used and not on combination effects.

Animals↗
PubMed1990

Aortic antioxidant defence mechanisms: time-related changes in cholesterol-fed rabbits.

In 24 rabbits fed a hyperlipidic diet (0.5% cholesterol, 5% lard and 5% peanut oil) for 10 (group A1), 30 group B1) and 60 days, (Group C1), compared to 24 control rabbits fed a standard diet for the same periods, antioxidant defence system (total superoxide dismutase, catalase, total thiol compounds selenium-dependent and selenium-independent glutathione peroxidase, glutathione reductase, glutathione transferase) and lipid peroxidation (thiobarbituric acid-reactive substances) in the aortic wall were tested. The percent of intima with grossly apparent atherosclerosis, is assessed by staining with the lipophilic dye Sudan IV, was negligible in group A1, but increased progressively in groups B1 (22.7-6.7%) and C1 (56.8-8.8%). Compared to the controls, a significant rise in superoxide dismutase activity was observed after 30 days of hyperlipidic diet, with a further marked increase at 60 days. Total thiol compounds and selenium-dependent glutathione peroxidase activity rose progressively from 10 to 30 and 60 days in cholesterol-fed rabbits. On the contrary, catalase, glutathione reductase and glutathione transferase activities significantly decreased in all experimental groups. Selenium-independent glutathione peroxidase activity was not detectable. Thiobarbituric acid-reactive substances increased about 3 times in hyperlipidemic rabbits. In conclusion, the changes in aortic antioxidant defence mechanisms and lipid peroxidation precede the massive vascular lipid infiltration in cholesterol-fed rabbits; some antioxidant mechanisms are stressed (superoxide, dismutase, glutathione peroxidase, total thiol compounds), whereas others are depressed (catalase, glutathione reductase, and glutathione transferase), thus potentially reducing or increasing vascular susceptibility to oxidative injury.

Animals↗
PubMed2001

Effects of fish oil and vitamin E on the antioxidant defense system in diet-induced hypercholesterolemic rabbits.

This study was designed to investigate the effects of fish oil and vitamin E on the antioxidant defense system in hypercholesterolemic rabbits. A high fat and cholesterol diet, with or without supplement by fish oil and/or a vitamin E supplement, was fed to rabbits for 6 weeks. Compared to the reference diet of regular laboratory rabbit chow, a high fat and cholesterol-enriched diet increased atheroma formation, plasma lipid and peroxide levels, decreased blood glutathione levels, and reduced plasma glutathione reductase, glutathione peroxidase, and catalase activities. Fish oil supplementation significantly reduced atheroma and increased glutathione reductase and glutathione peroxidase activities and blood glutathione levels, but increased plasma lipid peroxide levels. Vitamin E supplementation of the fish oil diet enhanced the beneficial effects by increasing glutathione reductase activity and decreasing peroxide levels. These results indicate that a high fat and cholesterol diet attenuates blood glutathione levels and plasma antioxidant enzyme activities, which may account for some of its atherogenic properties. Consumption of fish oil enhances antioxidative defenses against the oxidative stress imposed by hypercholesterolemia, and vitamin E further enhances these beneficial effects.

Animals↗
PubMed2005

Mammalian selenoprotein thioredoxin-glutathione reductase. Roles in disulfide bond formation and sperm maturation.

Thioredoxin reductases (TRs) are important redox regulatory enzymes, which control the redox state of thioredoxins. Mammals have cytosolic and mitochondrial TRs, which contain an essential selenocysteine residue and reduce cytosolic and mitochondrial thioredoxins. In addition, thioredoxin/glutathione reductase (TGR) was identified, which is a fusion of an N-terminal glutaredoxin domain and the TR module. Here we show that TGR is expressed at low levels in various tissues but accumulates in testes after puberty. The protein is particularly abundant in elongating spermatids at the site of mitochondrial sheath formation but is absent in mature sperm. We found that TGR can catalyze isomerization of protein and interprotein disulfide bonds and localized this function to its thiol domain. TGR targets include proteins that form structural components of the sperm, including glutathione peroxidase GPx4/PHGPx. Together, TGR and GPx4 can serve as a novel disulfide bond formation system. Both enzymes contain a catalytic selenocysteine consistent with the role of selenium in male reproduction.

Animals↗
PubMed1996

On Transition Structures for Hydride Transfer Step in Enzyme Catalysis. A Comparative Study on Models of Glutathione Reductase Derived from Semiempirical, HF, and DFT Methods.

As a model of the chemical reactions that take place in the active site of gluthatione reductase, the nature of the molecular mechanism for the hydride transfer step has been characterized by means of accurate quantum chemical characterizations of transition structures. The calculations have been carried out with analytical gradients at AM1 and PM3 semiempirical procedures, ab initio at HF level with 3-21G, 4-31G, 6-31G, and 6-31G basis sets and BP86 and BLYP as density functional methods. The results of this study suggest that the endo relative orientation on the substrate imposed by the active site is optimal in polarizing the C4-Ht bond and situating the system in the neighborhood of the quadratic region of the transition structure associated to the hydride transfer step on potential energy surface. The endo arrangement of the transition structure results in optimal frontier HOMO orbital interaction between NADH and FAD partners. The geometries of the transition structures and the corresponding transition vectors, that contain the fundamental information relating reactive fluctuation patterns, are model independent and weakly dependent on the level of theory used to determine them. A comparison between simple and complex molecular models shows that there is a minimal set of coordinates describing the essentials of hydride transfer step. The analysis of transition vector components suggests that the primary and secondary kinetic isotope effects can be strongly coupled, and this prompted the calculation of deuterium and tritium primary, secondary, and primary and secondary kinetic isotope effects. The results obtained agree well with experimental data and demonstrate this coupling.

Journal Article↗
PubMed1996

Antioxidants in hereditary pancreatitis.

OBJECTIVE: The cause of hereditary pancreatitis (HP) remains unknown. This study evaluated the hypothesis that patients with HP have genetically determined low concentrations of antioxidants that may predispose them to repetitive pancreatic injury. METHODS: This cross-sectional analysis compared antioxidant levels in four groups of patients. Group 1 included 14 related people with chronic pancreatitis. Group 2 (11 individuals) belonged to the same kindred but did not have pancreatitis. Group 3 was a group of 65 unrelated control subjects, and Group 4 consisted of seven unrelated children with chronic pancreatitis from other causes. The antioxidant levels analyzed included glutathione peroxidase, superoxide dismutase, glutathione reductase, glutathione transferase, selenium, and vitamin E. Amylase levels were measured in all patients in groups 1, 2, and 4. RESULTS: People with chronic pancreatitis or relatives of people with hereditary pancreatitis (groups 1, 2, and 4) had significantly lower mean glutathione peroxidase values than controls (group 3, p < 0.001). Group 1 also had significantly lower selenium levels than groups 2 and 3 (p < 0.001) but greater levels than group 4 (p = 0.029). Vitamin E levels were lower in group 1 than in groups 2 and 4. The superoxide dismutase levels were significantly different between each group (p < 0.001), and group 1 had the highest level. The glutathione reductase, glutathione transferase, and amylase levels did not differ significantly between groups. However, group 1 had a significantly higher glutathione transferase level than group 4. CONCLUSION: We identified antioxidant deficiencies in a group of patients with hereditary pancreatitis. Higher selenium and vitamin E levels may have prevented their relatives in group 2 from having pancreatitis secondary to oxidant injury, despite low glutathione peroxidase levels. Supplementation with selenium or vitamin E or both may be a beneficial therapeutic option in these patients to decrease the frequency of pancreatitis.

Adolescent↗
PubMed1990

[Histochemical and biochemical changes in skeletal muscles of rhabdomyolysis-sensitive racehorses following exertion. III: Elevated activity of various antioxidant enzymes].

In this communication, the results of a histochemical and biochemical enzyme study on gluteus medius muscle of horses, sensitive to exertional myopathy, during attacks of rhabdomyolysis are presented. For the biochemical study the biopsy specimens investigated were selected by means of histological and enzyme histochemical staining methods. Dissected specimens were used which contained groups of muscle fibres with a high or low activity of glucose-6-phosphate dehydrogenase. The activity of glucose-6-phosphate dehydrogenase, phosphogluconate dehydrogenase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase was measured microbiochemically in these dissected specimens. A rise in activity of glucose-6-phosphate dehydrogenase in pathologically changed muscle fibres was always found to be coupled with a significant rise in activity of phosphogluconate dehydrogenase, glutathione reductase, and glutathione peroxidase. In these muscle fibres, the activity of superoxide dismutase and catalase was not significantly increased. On the basis of the combined histochemical and biochemical findings it is concluded that the application of the histochemical method for the demonstration of glucose-6-phosphate dehydrogenase activity can be highly recommended for the study of antioxidant enzymes in skeletal muscles with neuromuscular defects.

Animals↗
PubMed1994

Developmental aspects of detoxifying enzymes in fish (Salmo iridaeus).

The activities of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione transferase and glyoxalase I have been studied during the embryologic development of rainbow trout (Salmo iridaeus) and in several other trout tissues to investigate the protective development metabolism. A gradual increase of superoxide dismutase, catalase, glutathione reductase, glyoxalase I and glutathione transferase activities was noted throughout embryo development. In all trout tissues investigated glutathione peroxidase was found to be extremely low compared to catalase activity. The highest activity of superoxide dismutase, glyoxalase I and glutathione reductase was found in liver followed by kidney. No change in the number of GST subunits was noted with the transition from the embryonic to the adult stages of life according to the SDS/PAGE and HPLC analyses performed on the GSH-affinity purified fractions.

Animals↗
PubMed2000

Thioredoxin reductase and glutathione synthesis is upregulated by t-butylhydroquinone in cortical astrocytes but not in cortical neurons.

The electron donors glutathione and thioredoxin play many vital roles in the mechanisms of cells to cope with oxidative stress. Critical to such antioxidant functions are the ability to synthesize glutathione and keep it reduced via glutathione reductase and the ability to reduce oxidized-thioredoxin via thioredoxin reductase. The rate-limiting enzyme for glutathione synthesis, gamma-glutamylcysteine synthase, is regulated by the antioxidant response element, whereas little is known about the regulation of expression of the selenoenzyme thioredoxin reductase. There were several objectives in this study. One was to determine whether the phase II enzyme inducer t-butylhydroquinone would increase thioredoxin reductase in neural cells; we found that both cytosolic and mitochondrial thioredoxin reductase activity and protein content is increased in cortical astrocytes, but not in cortical neurons. A second objective was to determine whether there are differences in the ability of t-butylhydroquinone to increase glutathione content in astrocytes and neurons; we found that glutathione is increased in astrocytes but not neurons. Finally, t-butylhydroquinone addition did not affect glutathione reductase activity in neurons and caused only a modest increase in astrocytes. Our findings emphasize the central role that astrocytes play in the antioxidant activities of the CNS. Our findings also suggest that thioredoxin reductase and gamma-glutamylcysteine synthase belong to the same synexpression group.

Animals↗
PubMed1992

Glutathione metabolic enzyme activities in diabetic platelets as a function of glycemic control.

Type 1 diabetic subjects categorized on the basis of the glycated haemoglobin content of their blood (low less than 7%; medium, greater than 7% and less than 11%; high, greater than 11%) were analyzed for total intraplatelet GSH as well as for the steady-state kinetic parameters (apparent KM and apparent Vmax) of some glutathione metabolic enzymes including glutathione reductase, glutathione peroxidase, gamma-glutamyltrans-peptidase and glutathione-S-transferase. This study indicates that intraplatelet GSH content of subjects with low glycated-haemoglobin is approximately 2-fold higher than those with medium glycated-haemoglobin. There was no further decrease in intraplatelet-GSH in subjects with high glycated-haemoglobin. The kinetic parameters of the platelet-enzymes studied (glutathione reductase, gamma-glutamyltranspeptidase and glutathione-S-transferase) were essentially independent of the glycation state of the subject. However, the apparent KM of glutathione peroxidase was approximately 4-fold higher in the subjects with high glycated-haemoglobin, in comparison to low subjects. This decrease in affinity could possibly result from the susceptibility of this enzyme to non-enzymatic glucosylation as purified samples of glutathione peroxidase incubated in vitro with glucose showed similar increases in apparent KM. These results are discussed in terms of the potential contribution of glutathione peroxidase impairment, to the hyperaggregability of the diabetic platelet.

Blood Platelets↗
PubMed1991

Glutathione and glutathione-metabolizing enzymes in the erythrocytes of healthy children and in children with insulin-dependent diabetes mellitus, juvenile rheumatoid arthritis, coeliac disease and acute lymphoblastic leukaemia.

Oxidative biotransformation of xenobiotics and endogenous substances involves glutathione in reduced form as an integral component through two mechanisms: glutathione peroxidase catalysing the reduction of hydrogen peroxide and organic hydroperoxides, and glutathione-S-transferases catalysing the conjugation of oxygenated derivatives with glutathione. We studied glutathione and glutathione-related enzyme activities in haemolysed venous blood samples from 49 healthy children and from 11 children with diabetes mellitus, 10 children with rheumatoid arthritis, seven children with active coeliac disease, and seven children with acute lymphoblastic leukaemia. Among the healthy children glutathione content and the activities of glutathione reductase, glutathione peroxidase, and glutathione-S-transferase were unrelated to sex; age-dependent differences were also minor. The patients with diabetes mellitus had decreased activity of glutathione reductase. The patients with acute lymphoblastic leukaemia had increased activity of both glutathione peroxidase and glutathione-S-transferase, possibly reflecting an adaptive response to free-radicals. The patients with active coeliac disease had control levels of all measured parameters of glutathione-related reactions indicating, since we earlier found decreased activities of glutathione peroxidase in intestinal mucosa of celiacs, that blood may not always reflect tissue-specific changes.

Adolescent↗
PubMed1986

Effects of long term alcohol ingestion on glutathione metabolising enzymes and taurine contents in the myocardium of rats.

The effects of long term intake of dietary alcohol on myocardial glutathione metabolism and taurine content were studied in rats. Alcohol, comprising more than 30% of the dietary calorie content, was administered to male CFY rats for six weeks. Compared with the controls, the left ventricle of the alcohol treated animals had an increased taurine content (18.4(2.6) vs 13.1(2.5) mumol X g wet weight-1) and a slightly, but not significantly, decreased reduced glutathione content. To assess the glutathione metabolism in the myocardium, the activities of glutathione reductase, glutathione peroxidase, glutathione-S-transferase, gamma-glutamylcysteine synthetase, and glutathione synthetase were measured. Significant increases were found in the activities of glutathione reductase (0.65(0.03) U.g wet weight-1 in the controls and 0.80(0.05) U.g wet weight-1 in the alcohol treated rats) and glutathione-peroxidase after six weeks of alcohol ingestion. Only slight, non-significant changes were found for the other enzymes investigated. It is thus apparent that in the myocardium of rats treated long term with ethanol the previously observed enhanced lipoperoxidation is not necessarily associated with severe glutathione depletion, and an increase in the activity of glutathione reductase might be responsible, at least in part, for the preservation of glutathione.

Alcoholism↗
PubMed1991

Aortic glutathione-related antioxidant defences in rabbits subjected to suprarenal aortic coarctation hypertension.

In seven rabbits subjected to suprarenal aortic coarctation hypertension, the segments above and below the coarctation were tested for the antioxidant defences (i.e. acid-soluble thiol compounds, selenium-dependent and selenium-independent glutathione peroxidase, glutathione reductase, glutathione transferase) and thiobarbituric acid-reactive substances. Seven sham-operated rabbits served as controls. Systolic blood pressure proximal to the ligature increased significantly with respect to pre-operative values after 16 days (117 +/- 8.3 vs 71.7 +/- 5.2 mmHg, P less than 0.05), while pressure distal to the ligature remained normotensive. Higher values of acid-soluble thiol compounds, thiobarbituric acid-reactive substances and increased activities of selenium-dependent glutathione peroxidase, glutathione reductase and glutathione transferase were assayed in the suprarenal with respect to the subrenal segment in both groups. However, the values of the upper segments were more elevated in the experimental group than in controls, but no differences were observed in the lower segments. Glutathione peroxidase activity assayed with cumene hydroperoxide was higher than the activity assayed with hydrogen peroxide in the hypertensive segments, but no differences were detected in the substenotic and control segments. Furthermore, an isoenzymatic form of glutathione transferase, analogous to rat 8-8 glutathione transferase isoenzyme, was detected by immunodiffusion in the hypertensive aorta. The following conclusions may be drawn: (1) a biochemical gradient in glutathione-related enzymes, acid-soluble thiol compounds and thiobarbituric acid-reactive substances between the proximal and distal aorta seems to exist in control rabbits; (2) suprarenal aortic coarctation induces a significant increase in glutathione-related antioxidant defences and thiobarbituric acid-reactive substances of the hypertensive aortic wall.

Animals↗
PubMed2001

Antioxidant imbalance in the lungs of cystic fibrosis transmembrane conductance regulator protein mutant mice.

Recent studies suggest that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein modulates epithelial reduced glutathione (GSH) transport and when defective creates an antioxidant imbalance. To test whether the CFTR protein modulates lung antioxidant defenses in vivo, epithelial lining fluid (ELF) and lung tissue from CFTR knockout (CFTR-KO) and wild-type (WT) mice were compared for GSH content and the activities of glutathione reductase, glutathione peroxidase, and gamma-glutamyltransferase. In the CFTR-KO mice, the ELF concentration of GSH was decreased (51%) compared with that in WT mice. The concentration of GSH in the lung tissue of CFTR-KO mice, however, was not significantly different from that in WT mice. The activities of glutathione reductase and glutathione peroxidase in the lung tissue of CFTR-KO mice were significantly increased compared with those in WT mice (48 and 28%, respectively). Tissue lipid and DNA oxidation were evaluated by measurement of thiobarbituric acid-reactive substances and 8-hydroxy-2'-deoxyguanosine, respectively. The levels of thiobarbituric acid-reactive substances and 8-hydroxy-2'-deoxyguanosine in the lung tissue of CFTR-KO mice were significantly increased compared with those in WT mice. These data support our hypothesis that a mutation in the CFTR gene can affect the antioxidant defenses in the lung and may contribute to the exaggerated inflammatory response observed in CF.

Animals↗