The activities of selected hepatic and renal drug-metabolizing enzymes of the ostrich, chicken and rats were compared. The concentration of glutathione in the liver and kidneys of the avian species was significantly lower than in the rat. The activity of ostrich hepatic glutathione S-transferase was 2-fold higher than that of ...

The level of lipid peroxidation products and the content of glutathione in erythrocytes of rats with Morris 5123 hepatoma at different stages of tumor development were examined. The content of endogenous malondialdehyde (MDA) was increased throughout all periods of tumor development as compared to the results for healthy rats. From ...

To confirm whether or not cytosolic NADPH-UQ reductase is involved in the recycling of cellular ubiquinol (UQH2) consumed during lipid peroxidation, the effect of a UQ-10 supplement on the NADPH-UQ reductase and cellular defense against oxidative damage in rat livers was investigated. Supplements of UQ-10 for 14 days enhanced the ...

1,2:3,4-Diepoxybutane (BDE) is probably the ultimate genotoxic metabolite of the rodent carcinogen 1,3-butadiene (BD). The formation of BDE from BD has been characterized in vitro using tissues from rats, mice, and humans. For assessment of human risk following exposure to BD, a quantitative understanding between the balance of formation and ...

The activities of superoxide dismutase (SOD), catalase glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-R) and the concentration of ascorbate, alpha-tocopherol, non-protein and protein-bound sulfhydryl compounds, and thiobarbituric acid-reactive substances (TBA-rs) in liver, erythrocytes and serum of rats dosed with 1.5 g methanol/kg bw were measured after 6, 12 and 24 ...

The objective of this study was to purify and characterize rat aortic glutathione S-transferases (GSTs) and to assess their role in the biotransformation of the nitrovasodilator, glyceryl trinitrate (GTN). Two class alpha GSTs (Ya and Yc) a class mu GST (Yb2) and a class pi GST (Yp) were identified in ...

Glutathione S-transferases (GSTs) provide protection to cells against electrophilic xenobiotics as well as lipid hydroperoxides and 4-hydroxynonenal generated during lipid peroxidation. The catalytic properties of the alpha class GSTs are well suited for detoxification of electrophilic products of lipid peroxidation. An immunologically distinct subgroup of the alpha class GST isozymes ...

A physiological toxicokinetic (PT) model is presented describing disposition and metabolism of 1,3-butadiene (BU) and 1,2-epoxy-3-butene (BMO) in rat, mouse and man, and of 1,2:3,4-diepoxybutane (BDI) in mice. It contains formation of BMO and BDI, intrahepatocellular first-pass hydrolysis of BMO, conjugation of BMO with glutathione (GSH) and GSH-turnover in the ...

1,3-Butadiene (BD) is a carcinogen in rats and mice. Previous in vitro studies showed that mouse liver microsomes formed 1,2-epoxy-3-butene (BMO) from BD and 1,2:3,4-diepoxybutane (BDE) from BMO at much higher rates than rat or human microsomes. Blood and tissue levels of BDE were significantly lower in rats than in ...

Tumor cell resistance against melphalan (LPAM) has been associated with increased cellular reduced glutathione (GSH) levels and glutathione S-transferase activity. Therefore, GSH conjugation of LPAM has been hypothesized to be a key factor in tumor cell resistance. In the present study, we evaluated GSH conjugation of LPAM by the perfused ...

Bromodichloromethane (BDCM), a carcinogenic water disinfection by-product, has been shown to be metabolized to intermediates that covalently bind to lipids and proteins, and this binding has been associated with trihalomethane-induced renal and hepatic toxicity. In this study, the effects of glutathione (GSH) on in vivo BDCM toxicity and in vitro ...

The biotransformation of the nephrotoxic fungicide chlorthalonil (2,4,5,6-tetrachloroisophthalonitril) has been studied in the rat and in rat liver subcellular fractions. In rat liver cytosol, chlorthalonil was rapidly transformed to 4,6-bis(glutathion-S-yl)-2,5-dichloroisophthalonitril in the presence of glutathione in a reaction catalysed by glutathione S-transferases. 4-(Glutathion-S-yl)-2,5,6-trichloroisiphthalonitril was observed as an intermedite in the ...

Glutathione (GSH) is a major antioxidant that protects tissues from free radical injury. 5-fluorouracil (5-FU) considered the most active antineoplastic agent in the treatment of advanced gastrointestinal malignancies, causes hepatic GSH depletion. Glutamine (GLN) augments host defenses and may be important in GSH synthesis. We hypothesized that alanyl-glutamine (ALA-GLN) may ...

The effects of hypoxia on glutathione (GSH) concentration and GSH-related enzyme and transport systems were studied in the small intestine of rats exposed to 8-10 days of 10.5% O2. Exposure to hypoxia resulted in a 40% lower GSH concentration in enterocytes and a 50% lower concentration in blood plasma. Activities ...

The effects of water-immersion restraint (WIR) stress on lipid peroxide, glutathione (GSH), glutathione peroxidase (GSH-Px), gamma-glutamylcysteine synthetase (gamma-GCS) and gamma-glutamyltranspeptidase (gamma-GT) activities in several tissues of rats were investigated. Hepatic and intestinal lipid peroxide levels were increased significantly in the WIR stress group. In both tissues, GSH levels were significantly ...

We found that NADPH-dependent ubiquinone reductase (NADPH-UQ reductase) in rat liver cytosol reduces ubiquinone (UQ) to ubiquinol (UQH2) in lipid membranes and consequently inhibits lipid peroxidation [Takahashi T., et al., Biochem. J., 309, 883-890 (1995)]. Here we examined whether or not this UQH2-regenerating system functions as a cellular antioxidant defense ...

AIM: To study the effects of beta-carotene (Car) reducing the cardiotoxicity induced by doxorubicin (Dox). METHODS: The pathological changes of rat myocardium were observed with photomicroscopy. The malondialdehyde (MDA) value of rat heart was measured with thiobarbituric acid method. The pyrogallol autoxidation method was used for determination of superoxide dismutase ...

The influences of food deprivation and refeeding on glutathione (GSH) status, antioxidant enzyme activity and lipid peroxidation in response to an acute bout of exercise were investigated in the liver and skeletal muscles of male Sprague-Dawley rats randomly divided into three groups: starved for 48 h without refeeding; starved for ...

Treatment of rats with a lignan-enriched extract of the fruit of Schisandra chinensis could enhance hepatic antioxidant/detoxification system, as indicated by increases in hepatic reduced glutathione (GSH) level as well as hepatic glutathione reductase and glutathione S-transferase activities. The hepatoprotective action was evident after aflatoxin beta 1 or cadmium chloride ...

In isolated hepatocytes, cystathionine, methionine, and thioether analogues of methionine, cysteine, and homocysteine, including S-adenosyl derivatives, inhibited reduced glutathione (GSH) efflux. The potency of inhibition by thioethers with different S-alkyl moieties was methyl < ethyl < butyryl < aminoethyl < alpha-aminopropionyl. Inhibition of GSH efflux by cystathionine from hepatocytes that ...

The interplay between bioactivation and inactivation functions of human erythrocytes and rat liver was studied. Glutathione depletion was used as a measure of the amount of reduced glutathione (GSH)-reactive compound. Iodoacetamide (IAcA), N-ethylmaleimide (NEM) and diethyl maleate (DEM), which are electrophiles that need no metabolic activation, were able to deplete ...

Oltipraz (OPZ) is currently being considered for human use to protect against aflatoxin B1 (AFB)-induced hepatocarcinogenesis based on its proven protective effect in rats. The effectiveness of this treatment presumes that orthologous cytochrome P450 and glutathione S-transferase (GST) isozymes metabolize AFB in humans as they do in rats. In this ...

In this investigation, the activities of five enzymes (catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glucose-6-dehydrogenase) involved in oxygen radical (OR)-detoxification and antioxidative defense were measured in conjunction with an index of lipid peroxidation in major prostatic lobes of young (2 month-old) and old (9 month-old) rats. Selective decreases in ...

A marked age-related decrease in glutathione (GSH) levels as well as depression of gamma-glutamylcysteine synthetase activity are factors that are believed to render the aged lens more susceptible to oxidative stress and, therefore, to cataractogenesis. Providing gamma-L-glutamyl-L-cysteine, the dipeptide precursor of GSH, would effectively bypass the compromised first step in ...

PURPOSES: To assess the efficacy of 2-mercaptoethanol/L-cysteine mixed disulfide (CySSME) as an L-cysteine prodrug suitable for glutathione biosynthesis in rat lenses in vitro, as an agent for the prevention of acetaminophen- and naphthalene-induced murine cataract in genetically-susceptible mice, and as an agent for maintenance of near-normal glutathione levels in lenses ...

The cytotoxicity of 2-bromoethanol towards hepatocytes isolated from rats was concentration-dependent (EC(50)100 mu M, 2 hr). Bromoacetaldehyde was more toxic (EC(50)60 mu M, 2 hr) and bromoacetic acid was less toxic (EC(50)150 mu M, 2 hr). Glutathione (GSH) depletion occurred before cytotoxicity ensued and GSH depleted hepatocytes were more susceptible ...

Glutathione levels are decreased in the substantia nigra of patients with Parkinson's disease. We studied whether glutathione depletion contributes to dopaminergic cell death using a specific inhibitor of glutathione biosynthesis, L-buthionine sulfoximine (BSO). We found no significant reduction of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta (SNpc) when ...

Cytosolic glutathione S-transferases (GSTs) from rat kidneys were purified by a combination of glutathione and S-hexylglutathione affinity columns. The isolated GSTs were subjected to reverse-phase HPLC and electrospray MS analysis. The major GST isoenzymes expressed in kidney are subunits 1, 2, 7 and 8. GST 1',3 and 4 are expressed ...

Glutathione S-transferases (GSTs) play a major role in the (de-)toxification of many endogenous and xenobiotic substrates. To assess their contribution in (de-)toxification, specific in vivo inhibitors that ideally are selective for a single isoenzyme of GST are required. In the present study, selective inhibition of the alpha class GST by ...

(R,S)-3-Hydroxy-4-pentenoate rapidly and selectively depletes the mitochondrial glutathione pool in rat hepatocytes, but shows little cytotoxicity and does not induce mitochondrial dysfunction [Shan, X., et al. (1993) Chem. Res. Toxicol. 6, 75-81]. The objective of the present studies was to investigate the 3-hydroxybutanoate dehydrogenase-dependent oxidation of (R)- and (S)-3-hydroxy-4-pentenoate and ...

Increased intake of Cd results in its retention and in peroxidative damage in soft tissues. Coadministration of antioxidants, viz., glutathione (GSH), alpha-tocopherol, and Se, restricted the uptake and distribution of Cd in liver and kidney of rats. Moreover, no rise in malondialdehyde was recorded. Although possible antioxidative mechanisms manifested by ...

1,3-Butadiene (BD) has been classified as a probable human carcinogen based on sufficient evidence of a carcinogenic response in B6C3F1 mice and Sprague-Dawley rats and limited human evidence of carcinogenicity. Mice are much more susceptible to BD-induced carcinogenicity than rats. Previous in vitro studies revealed that mouse liver microsomes formed ...

Mitochondria may be primary targets of free radical damage associated with aging. We have found that mitochondrial glutathione is markedly oxidized with aging in rats and mice. The oxidized to reduced glutathione ratio rises with aging in the liver, kidney, and brain. The magnitude of these changes is much higher ...

The stability of curcumin, as well as the interactions between curcumin and cytochrome P450s (P450s) and glutathione S-transferases (GSTs) in rat liver, were studied. Curcumin is relatively unstable in phosphate buffer at pH 7.4. The stability of curcumin was strongly improved by lowering the pH or by adding glutathione (GSH), ...

The irreversible and reversible inhibition of glutathione S-transferases (GSTs) by eugenol was studied in rat, mouse and man. Using liver cytosol of human, rat and mouse, species differences were found in the rate of irreversible inhibition of GSTs by eugenol in the presence of the enzyme tyrosinase. Tyrosinase was used ...

Potential lead exposure to the eyes as a result of the use of traditional cosmetic Kohl in Asia, Africa and the Middle East has been a subject of recent debate to the scientific community. In continuation of our earlier work we therefore examine in the present study, the drug metabolic ...

Five phenolic compounds, namely caffeic acid, sesamol, hydroquinone, catechol, and 4-methoxyphenol, were fed to groups of 30 male F344 rats at dietary levels of 2, 2, 0.3, 0.8, and 2%, respectively, for 2 years. Retardation of body weight and elevated relative liver weights were noted for all groups. Formalin-fixed and ...

The purpose of the study was to investigate the effects of parathyroid hormone (PTH) infusion on antioxidant enzyme activity and lipid peroxidation of erythrocytes in five-sixths nephrectomized (Nx) rats. Five-sixths Nx rats had a higher osmotic fragility in red blood cells (RBC). Thyroparathyroidectomy (TPTX) effectively decreased the abnormality of osmotic ...

Hepatoprotective effect of Tamra bhasma has been studied on cumene hydroperoxide (CHP) induced peroxidation, reduced glutathione content and superoxide dismutase (SOD)-in rat liver homogenate. The drug was orally given for 8 days which showed significant reduction in the level of malondialdehyde (MDA) production at different concentrations of cumene hydroperoxide in ...

The protective effects of lobenzarit, an antioxidative agent and antirheumatic drug, on the cytotoxicity of paracetamol in rat hepatocytes were studied, as well as the inhibitory effects of lobenzarit on cytochrome P-450s and glutathione S-transferases (GSTs) in rat liver. Paracetamol was selected as a model toxin, since it is known ...

Wild Norway rats (Rattus norvegicus) were collected from a site contaminated by a range of polycyclic aromatic hydrocarbons (PAHs), mineral oils, polychlorobiphenyls (PCBs) and heavy metals. Activities of cytochrome P450 monooxygenases (ethoxy-, pentoxy- and benzoxy-resorufin O-dealkylases, and 4-nitrophenol hydroxylase) were measured in microsomal fractions from liver and lung. Antioxidant enzyme ...

When weanling male rats of the Wistar strain were fed a selenium-deficient diet, the activity of classic glutathione peroxidase (GPx) in liver cytosol decreased rapidly. In contrast, the activity of phospholipid hydroperoxide GPx (PHGPx) in the cytosol decreased only slowly. Despite the marked decrease in classic GPx activity, the lipid ...

The comparative importance of phospholipid hydroperoxide glutathione peroxidase (PHGPx) and of "classic" glutathione peroxidase (GPx) in the reduction of phospholipid hydroperoxides is unclear. Although GPx activity is 500-fold higher than that of PHGPx in rat liver, the reduction of phospholipid hydroperoxides by glutathione (GSH) through GPx may be strongly limited ...

To determine how lipid peroxides and free radical scavengers are changed in the brain of hyper- or hypothyroid rats, we examined the behavior of lipid peroxide and free radical scavengers in the cerebral cortex of aged (1.5 years old) rats that had been made hyper- or hypothyroid by the administration ...

The effects of acarbose on cataract development, lens aldose reductase (EC 1.1.1.21) activity and lenticular reduced-glutathione content in diabetic sand rats (Psammomys obesus) were determined. Diabetic sand rats (diet-induced) were fed on diets with or without acarbose (0.4 g/kg) for 39 d. Daily plasma glucose, cataract incidence, aldose reductase and ...

The present study was envisaged to investigate the protective effects of zinc treatment on the activities of various drug metabolizing enzymes, reduced glutathione content, and extent of lipid peroxidation in the livers of male albino rats subjected to long-term carbontetrachloride (CCl4) toxicity. It was observed that the activities of cytochrome ...

Benzene is a human carcinogen; exposure to benzene can result in aplastic anemia and leukemia. Data from animal models are frequently used in the risk assessment for benzene. In rodent studies, mice have been shown to be more sensitive to benzene-induced hematotoxicity than rats. In this regard, we have observed ...

Disulfiram (CAS 97-77-8, DSF), a potent anticarcinogenic compound, is known to form mixed disulfides with sulfhydryl group containing amino acids or proteins in vivo. In the present study the stabilities of two mixed disulfides which may arise in the metabolism of disulfiram, i.e. S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine (AC-DDTC) and S-(N,N-diethyldithiocarbamoyl)-L-glutathione (GS-DDTC) in phosphate ...

The metabolism of 1,2-dibromo-3-chloropropane (DBCP), measured as the formation of water soluble metabolites and metabolites covalently bound to macromolecules, was studied in isolated rat liver, kidney, and testicular cells, in subcellular fractions, and with purified rat and human glutathione S-transferases (GSTs). The rate of formation of water soluble metabolites in ...

Alteration in glutathione S-transferase (GST) isoenzymes was compared with that of a peroxisomal enzyme, enoyl-CoA hydratase (ECH), during hepatocarcinogenesis caused by clofibrate (CF) administration in male Sprague-Dawley rats. The amount of alpha class GST forms, determined by single radial immunodiffusion using anti-GST 1-2 antibody, was inversely correlated with that of ...