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PubMed2000

Suppressive effect of curcumin on trichloroethylene-induced oxidative stress.

In vivo antioxidative effects of curcumin were investigated using a trichloroethylene (TCE)-induced oxidative stress model in mouse liver. Increases in the contents of peroxisome and thiobarbituric acid reactive substances (TBARS) and decreases in GSH content of mouse liver by the TCE administration were suppressed by the pre-administration of curcumin. TCE-induced changes in the activities of antioxidative enzyme, such as Cu/Zn-SOD, catalase, glutathione reductase. glutathione peroxidase (GPx) and D-glucose-6-phosphate dehydrogenase (G6PD), were also diminished by curcumin. These results indicate that curcumin significantly suppresses TCE-induced oxidative stress by scavenging various free radicals, and its antioxidative activity seems to be derived from its suppressive effects on the increase in peroxisome content and decrease in GPx and G6PD activities.

Animals↗

PubMed2005

Mechanisms underlying resistance of pancreatic islets from ALR/Lt mice to cytokine-induced destruction.

Nuclear and mitochondrial genomes combine in ALR/Lt mice to produce systemically elevated defenses against free radical damage, rendering these mice resistant to immune-mediated pancreatic islet destruction. We analyzed the mechanism whereby isolated islets from ALR mice resisted proinflammatory stress mediated by combined cytokines (IL-1beta, TNF-alpha, and IFN-gamma) in vitro. Such damage entails both superoxide and NO radical generation, as well as peroxynitrite, resulting from their combination. In contrast to islets from other mouse strains, ALR islets expressed constitutively higher glutathione reductase, glutathione peroxidase, and higher ratios of reduced to oxidized glutathione. Following incubation with combined cytokines, islets from control strains produced significantly higher levels of hydrogen peroxide and NO than islets from ALR mice. Nitrotyrosine was generated in NOD and C3H/HeJ islets but not by ALR islets. Western blot analysis showed that combined cytokines up-regulated the NF-kappaB inducible NO synthase in NOD-Rag and C3H/HeJ islets but not in ALR islets. This inability of cytokine-treated ALR islets to up-regulate inducible NO synthase and produce NO correlated both with reduced kinetics of IkappaB degradation and with markedly suppressed NF-kappaB p65 nuclear translocation. Hence, ALR/Lt islets resist cytokine-induced diabetogenic stress through enhanced dissipation and/or suppressed formation of reactive oxygen and nitrogen species, impaired IkappaB degradation, and blunted NF-kappaB activation. Nitrotyrosylation of beta cell proteins may generate neoantigens; therefore, resistance of ALR islets to nitrotyrosine formation may, in part, explain why ALR mice are resistant to type 1 diabetes when reconstituted with a NOD immune system.

Active Transport, Cell Nucleus↗

PubMed2003

Free radical toxicity and antioxidants in Parkinson's disease.

Erythrocyte lipid peroxidation, oxidative hemolysis, erythrocyte antioxidant enzymes, viz. superoxide dismutase, glutathione reductase, glutathione peroxidase, catalase and plasma antioxidants, viz. vitamin A, vitamin E, vitamin C and ceruloplasmin have been determined by spectrophotometric methods in 15 patients with Parkinson's disease (PD) and in 50 controls. Lipid peroxidation, oxidative hemolysis and plasma ceruloplasmin were significantly higher in PD patients as compared to normals. Erythrocyte antioxidants in PD patients were not significantly different from the controls. However, plasma vitamin C in PD patients was significantly lower than the controls. It is concluded that these patients are under oxidative stress which points to a possible involvement of free radicals in PD.

Adult↗

PubMed2004

The histone deacetylase inhibitor sodium butyrate induces breast cancer cell apoptosis through diverse cytotoxic actions including glutathione depletion and oxidative stress.

Sodium butyrate (NaBu), a potent histone deacetylase inhibitor, modulates the expression of a large number of genes. The purpose of this study was to determine whether this dietary agent could induce apoptosis in MCF-7 cells, a breast cancer cell line that lacks caspase-3 activity, and to identify the mechanisms that underlie NaBu toxicity in these cells. Cell viability assessed by the activity of mitochondrial succinate dehydrogenase (MTT assay) revealed a dose-dependent reduction of MCF-7 cellular growth in response to NaBu treatment. Restoring caspase-3 function by transfection did not modify NaBu toxicity in these cells. Following a 24-h exposure, NaBu-induced cell growth arrest in G2/M phase in a dose-dependent fashion in association with stable expression of CDC25A, a G1-specific regulator of the cell cycle. The anti-proliferative effects of NaBu were accompanied by diminished expression of p53. Similarly, mRNA encoding c-Myc, a well-known regulator of p53, was decreased in NaBu-treated cells, while p21(Waf1/Cip1) mRNA was increased. Furthermore, bax mRNA level was up-regulated whereas a decline in Bcl-2 both protein and mRNA levels were detected in NaBu-treated cells. Apoptosis was observed following a treatment with 2 mM NaBu, reflected by Annexin-V staining and by the cleavage of poly(ADP-ribose) polymerase, whereas DNA laddering was absent. Apoptosis was associated with a pronounced depletion of intracellular glutathione levels. Finally, NaBu treatment significantly increased the activities of several antioxidant enzymes, including glutathione reductase, glutathione peroxidase, and catalase. Together, these data suggest that the pro-apoptotic effects of NaBu observed in MCF-7 cells are associated with oxidative stress.

Antioxidants↗

PubMed1989

Characterization of a cisplatin-resistant subline of murine RIF-1 cells and reversal of drug resistance by hyperthermia.

The development of tumor cell drug resistance is a major obstacle which often leads to failure of cancer chemotherapy. Therefore, reversing the cell drug resistance would have important implications in cancer treatment. We have developed a cisplatin-resistant mouse tumor cell line from the radiation induced fibrosarcoma (RIF-1) parental line; this line is named RIF/ptr1 versus the parental line RIF/pts1. It is shown that the formation of cisplatin-DNA interstrand cross-links is the same for both cell lines although the intracellular cisplatin concentrations of resistant line is significantly lower. The cytosolic activities of glutathione reductase, glutathione peroxidase, and DT-diaphorase were the same in two cell lines. However, the concentration of glutathione was significantly higher in the resistant line. The resistant line was shown to be more sensitive to the cytotoxicity of heat (43 degrees C) but the combination of heat and drug had the same tumoricidal effect for both cell lines. The addition of verapamil also had a similar effect on both cell lines. We conclude that the major difference between these two lines was the glutathione-related detoxification of platinum. Regardless of drug resistance, the combination of drug and heat can effectively kill both cell lines. Elevated glutathione in RIF/ptr1 cells may be associated both with enhanced heat sensitivity and drug resistance such that combined treatments with drug and heat were equally effective in killing cells of either line.

Animals↗

PubMed1988

Sequence of thioredoxin reductase from Escherichia coli. Relationship to other flavoprotein disulfide oxidoreductases.

The DNA sequence of the Escherichia coli gene encoding thioredoxin reductase has been determined. The predicted protein sequence agrees with an earlier determination of the 17 amino-terminal amino acids and with a fragment of the protein containing the redox-active half-cystines. Similarity between E. coli thioredoxin reductase and other flavoprotein disulfide oxidoreductases is quite limited, but three short segments, two of which are probably involved in FAD and NADPH binding, are highly conserved between thioredoxin reductase, glutathione reductase, dihydrolipoamide dehydrogenase, and mercuric reductase.

Amino Acid Sequence↗

PubMed1987

Changes in protein sulfur groups in hepatocytes of newborn rats under glucocorticoid stimulation.

A daily administration of hydrocortisone-acetate (25 micrograms/g b.w.) increased both dry mass and protein content of the hepatocytes of newborn rats by 84% and 89% respectively, after 5-day-treatment. The increase correlated with the duration of hormonal treatment. As an average per cell, the total reactive protein sulfur increased up to 127%. This increase depends on a major increment of thiols (+179%) and on a minor increment of disulfides (+18%). Within the thiols, the fast reactive ones exhibited the most pronounced increment (+214%). Per protein unit, the total reactive sulfur increased, after a 1 day lag period, by up to +20%. Thiols showed a 47%-increment due to increase of fast reactive thiols (+70%) more than of slow reactive thiols (+20%). On the contrary, disulfides decreased (-37%). Consequently, the protein thiol/disulfide ratio shifted from 2.14 in control hepatocytes to 4.98 (+133%) in hormone-stimulated hepatocytes. Both the increase of the thiol content, and the shift of the SH/SS-equilibrium of the cellular proteins, correlated with a concomitant increase of enzymic activities such as gamma-glutamyltranspeptidase, glutathione reductase, glutathione peroxidase, glutathione S-transferase and 7-ethoxycoumarin O-deethylase.

Age Factors↗

PubMed1996

Role of Murraya koenigii (curry leaf) and Brassica juncea (Mustard) in lipid peroxidation.

The status of lipid peroxidation was investigated in rats fed M. Koenigii (curry leaf) and B. juncea (Mustard). Concentration of malondialdehyde showed a significant decrease, while hydroperoxides and conjugated dienes were significantly increased in liver and heart of both the experimental groups. SOD and catalase activity was found to be increased in liver and heart of both the spices administered groups. Glutathione levels in liver, heart and kidney were lowered in rats administered these spices. Glutathione reductase, glutathione peroxidase and glutathione S-transferase activity showed a sharp increase in the experimental groups compared to the controls.

Animals↗

PubMed1984

Mechanism of lipid peroxide formation in polychlorinated biphenyls (PCB) and dichlorodiphenyltrichloroethane (DDT)-poisoned rats.

To clarify the mechanism of lipid peroxide formation in polychlorinated biphenyls (PCB)-poisoned rats, the following two experiments were carried out. Experiment No. 1: Rats were separated into three groups. Group 1 was fed a normal diet, group 2 was fed a PCB-supplemented diet, and group 3 was fed a dichlorodiphenyltrichloroethane (DDT)-supplemented diet. After 5 months, the rats were killed. The thiobarbituric acid (TBA) values in livers of the PCB- and DDT-exposed rats had increased. The activity of catalase was increased in the PCB-fed rats but decreased after the administered of DDT. The glutathione peroxidase activity was decreased only in the PCB-administered rats. These results indicate that PCB and DDT have some effects to enhance lipid oxidation. It is probable that the decrease in glutathione peroxidase is the major reason for the increase of lipid oxidation in PCB-poisoned rats. The mechanism of lipid peroxidate production in DDT-poisoned rats could be different from the case of PCB poisoning. Experiment No. 2: Rats were separated into two groups. To one group, normal diet was given and to the other group PCB-supplemented diet was given. After 1 month, the rats were killed. In PCB-exposed rats, activities of glutathione reductase and glutathione S-transferase were increased. The increase in glutathione reductase and glutathione S-transferase were increased. The increase in glutathione reductase could be a compensation for a decrease in glutathione peroxidase. It is probable that PCB is metabolized to make glutathione conjugates by the action of glutathione S-transferase.

Animals↗

PubMed2001

Effect of high altitude (7,620 m) exposure on glutathione and related metabolism in rats.

Reduced and oxidised glutathione (GSH and GSSG) contents, and glutathione reductase, and glutathione S-transferase activities were studied in the livers, muscles, and blood/erythrocytes of male Sprague-Dawley rats exposed to intermittent hypoxia (6 h.day-1) at a simulated altitude of 7,620 m for 1, 7, 14, and 21 days. Significant decreases in GSH and increases in GSSG contents were observed in the muscles and blood of hypoxia-exposed rats in comparison to unexposed rats. Significant declines in GSH content by 43% and 45% respectively in muscles and blood were observed in the group exposed for 1 day which tended to recover on subsequent exposure. Glutathione reductase and glutathione S-transferase activities were decreased in the livers and erythrocytes of hypoxia-exposed rats, but were increased significantly in muscle. Lipid peroxidation was also increased in the livers and muscles of exposed rats. The changes were indicative of an increased production of reactive oxygen species and an impairment of drug and xenobiotic metabolism during exposure to high altitude hypoxia.

Acclimatization↗

PubMed2002

Increased methylglyoxal and oxidative stress in hypertensive rat vascular smooth muscle cells.

Methylglyoxal can yield advanced glycation end products via nonenzymatic glycation of proteins. Whether methylglyoxal contributes to the pathogenesis of hypertension has not been clear. The aim of the present study was to investigate whether the levels of methylglyoxal and methylglyoxal-induced advanced glycation end products were enhanced and whether methylglyoxal increased oxidative stress, activated nuclear factor-kappaB (NF-kappaB), and increased intracellular adhesion molecule-1 (ICAM-1) content in vascular smooth muscle cells from spontaneously hypertensive rats. Basal cellular levels of methylglyoxal and advanced glycation end products were more than 2-fold higher (P<0.05) in cells from hypertensive rats than from normotensive Wistar-Kyoto rats. This correlated with levels of oxidative stress and oxidized glutathione that were significantly higher in cells from hypertensive rats, whereas levels of glutathione and activities of glutathione reductase and glutathione peroxidase were significantly lower. Basal levels of nuclearly localized NF-kappaB p65 and ICAM-1 protein expression were higher in cells from hypertensive rats than from normotensive rats. Addition of exogenous methylglyoxal to the cultures induced a greater increase in oxidative stress and advanced glycation end products in cells from hypertensive rats compared with normotensive rats and significantly decreased the activities of glutathione reductase and glutathione peroxidase in cells of both rat strains. Methylglyoxal activated NF-kappaB p65 and increased ICAM-1 expression in hypertensive cells, which was inhibited by N-acetylcysteine. Our study demonstrates an elevated methylglyoxal level and advanced glycation end products in cells from hypertensive rats, and methylglyoxal increases oxidative stress, activates NF-kappaB, and enhances ICAM-1 expression. Our findings suggest that that elevated methylglyoxal and associated oxidative stress possibly contribute to the pathogenesis of hypertension.

Animals↗

PubMed2002

Protective role of L-methionine against free radical damage of rat brain synaptosomes.

Incubation of rat brain synaptosomal/mitochondrial fraction with tert-butylhydroperoxide resulted in accumulation of the lipid peroxidation product, conjugated dienes, damage of the synaptosomal membrane as evidenced by leakage of lactate dehydrogenase, and decrease of the total content of glutathione and of the GSH/GSSG ratio. This treatment also produced a considerable decrease of the ouabain-sensitive ATPase activity and a much smaller diminution of the activities of glutathione reductase and glutathione transferase. Preincubation of the synaptosomal/mitochondrial fraction with 0.5 or 1.0 mM L-methionine significantly protected against lipid peroxidation, membrane damage and changes in the glutathione system produced by low (1 mM) concentrations of tert-butylhydroperoxide and completely prevented inactivation of ouabain-sensitive ATPase, glutathione reductase and glutathione transferase by such treatment. The importance of L-methionine in antioxidant protection is discussed.

Animals↗

PubMed1998

Biochemical evaluation of oxidative stress in propylthiouracil treated hyperthyroid patients. Effects of vitamin C supplementation.

In this study the impact of vitamin C supplementation on oxidative damage as assessed by thiobarbituric acid reactive substances and markers of antioxidant status: namely Cu/Zn superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione were investigated in 24 hyperthyroid patients under propylthiouracil therapy (3x100 mg/day) for five days and in 15 healthy controls. Ascorbic acid (1000 mg/day) was given as a supplement for 1 month to both the patients and controls during the study period. Heparinised blood samples were taken at the beginning and the end of one month ascorbic acid supplementation. Comparison of the hyperthyroid patients with the controls revealed higher lipid peroxidation (p<0.001), higher Cu/Zn superoxide dismutase activity (p<0.001), higher glutathione level (p<0.001) and lower glutathione reductase activity (p<0.001). Vitamin C supplementation to hyperthyroid patients caused significant increases in glutathione concentration (p<0.001) and glutathione peroxidase activity (p<0.001), whereas there were significant decreases in glutathione reductase (p<0.001) and Cu/Zn superoxide dismutase activities (p<0.01). Thiobarbituric acid reactive substances and thiobarbituric acid reactive substances/glutathione ratio were significantly decreased (p<0.01). Vitamin C supplementation to euthyroid controls caused significant increases in glutathione concentration (p<0.001) and glutathione peroxidase and Cu/Zn superoxide dismutase activities (p<0.001), whereas there was a significant decrease in glutathione reductase (p<0.001). The thiobarbituric acid reactive substances/glutathione ratio was significantly decreased (p<0.05). Our findings reveal the potentiation of antioxidant status and a relief in oxidative stress in both propylthiouracil treated hyperthyroid patients and controls in response to vitamin C supplementation.

Adult↗

PubMed2003

Bisphenol A induces reactive oxygen species generation in the liver of male rats.

Bisphenol A, an environmental contaminant, widely used as a monomer in polycarbonate plastics, has been shown to cause abnormalities in liver of rats and mice. The nature and mechanism of action of bisphenol A on liver is not clear. The aim of the present study was to investigate if bisphenol A induces oxidative stress in the liver of rats and if co-administration of vitamin C, an antioxidant, can prevent oxidative stress. Bisphenol A (0.2, 2.0 and 20 micro g/kg body weight per day) and bisphenol A+vitamin C (0.2, 2.0, 20 micro g+40 mg/kg body weight per day) was orally administered to rats for 30 days. After 24 h of the last treatment, rats were killed using overdose of anesthetic ether. Body weights of the animals and the weights of liver showed no significant changes. The activities of antioxidant enzymes, superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase were decreased in mitochondrial and microsome-rich fractions of liver. The levels of hydrogen peroxide and lipid peroxidation increased in the treated rats when compared with the corresponding group of control animals. Activity of alanine transaminase, a marker enzyme of hepatic injury remained unchanged in the treated rats as compared with the corresponding control rats. Co-administration of bisphenol A and vitamin C showed no changes in the activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase and in the levels of hydrogen peroxide and lipid peroxidation as compared with the corresponding control groups. The results indicated that bisphenol A induces oxidative stress in the liver of rats by decreasing the antioxidant enzymes. Co-administration of vitamin C reversed the effects of bisphenol A-induced oxidative stress in the liver of rats.

Air Pollutants↗

PubMed2007

Induction of oxidative cell damage by photo-treatment with zinc meta N-methylpyridylporphyrin.

We have previously reported that isomeric Zn(II) N-methylpyridylporphyrins (ZnTM-2(3,4)-PyP4 + ) can act as photosensitizers with efficacy comparable to that of hematoporphyrin derivative (HpD) in preventing cell proliferation and causing cell death in vitro. To better understand the biochemical basis of this activity, the effects of photo-activated ZnTM-3-PyP4 + on GSH/GSSG ratio, lipid peroxidation, membrane permeability, oxidative DNA damage, and the activities of SOD, catalase, glutathione reductase, and glutathione peroxidase were evaluated. Light exposure of ZnTM-3-PyP4 + -treated colon adenocarcinoma cells caused a wide spectrum of oxidative damage including depletion of GSH, inactivation of glutathione reductase and glutathione peroxidase, oxidative DNA damage and peroxidation of membrane lipids. Cell staining with Hoechst-33342 showed morphological changes consistent with both necrotic and apoptotic death sequences, depending upon the presence of oxygen.

Catalase↗

PubMed1998

Sulphydryl groups and their relation to the antioxidant enzymes of chelonian red blood cells.

Thiol groups of hemoglobin and blood glutathione are higher in Geochelone carbonaria than in Geochelone denticulata. Exposure of stripped hemolysate of both tortoises to terc-butyl hydroperoxide, resulted in a higher ferroheme oxidation of G. denticulata hemoglobin. In this example glutathione reductase and glutathione peroxidase, were not active due to the absence of GSH and NADPH, suggesting that the thiol groups of G. carbonaria hemoglobin act as antioxidant, similar to GSH. In the total hemolysate, however, where the antioxidant enzymes are active, both species showed similar levels of hemoglobin oxidation, suggesting that the protective effect of thiol groups of hemoglobin are less effective for heme protection. The activity of glutathione reductase and glutathione peroxidase was higher in erythrocytes of G. denticulata and the activity of catalase and superoxide dismutase was higher in erythrocytes of G. carbonaria.

Animals↗

PubMedDate not supplied

[Effect of indomethacin and voltaren on glutathione oxidation and reduction in the liver of white rats].

It has been established that oral administration of indomethacin (2.5 mg/kg) to albino rats for one week leads to a decline in the level of reduced and an increase in the level of oxidized glutathione with a simultaneous activation of liver glutathione reductase and glutathione peroxidase. Administration of the drug for two weeks makes the indicators under study return in the main to normal. The raising of the drug dose up to 5 mg/kg makes the total content of glutathione fall at the expense of its reduced form. The activity of the enzymes significantly rises in all the observation periods (days 1-5 after administration). The use of voltaren in doses of 2.5 and 5 mg/kg does not produce any action on the glutathione forms or glutathione reductase and glutathione peroxidase activity in the liver.

Animals↗

PubMed1983

Response of the lens to oxidative-osmotic stress.

Both aldose reductase and glutathione reductase share a common cofactor, NADPH. Glutathione reductase is preferentially activated due to its higher affinity for the cofactor. Since NADPH is primarily consumed by glutathione reductase, which in conjunction with glutathione peroxidase detoxifies H2O2 present in the aqueous humor, the cataractogenic role of sorbitol-induced osmotic pressure must therefore depend on the availability of NADPH for aldose reductase activity. We examined the response of the lens to an oxidative-osmotic double stress and found that the lens indeed produced 79% less sorbitol and 45% less fructose than a lens subjected to the osmotic stress alone. Morphological studies showed that photo-oxidation damaged the epithelium where the cation pump resided. However, with additional osmotic stress, the swelling of lens fibers in the posterior pole region became more pronounced, and cell nuclei deep in the lens nuclear bow were dislodged to the posterior pole. This could be explained by the slight but significant loss of K+ in the lenses under the double stress. Apparently, the slightly decreased 86Rb uptake (26% loss), caused by photooxidation could not maintain adequate ionic balance even though the stress from accumulation of sorbitol + fructose was sub-maximal. No disturbance in the glycolytic activity or to the 86Rb efflux was found in these lenses, however.

Animals↗