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V B Junqueira

Publications and source records attributed to V B Junqueira.

36 records · Page 2Linked to original sources
PubMed1994

Dose-dependent study of liver lipid peroxidation related parameters in rats treated with pp'-DDT.

Rats treated with increasing doses of pp'-DDT (60, 100 and 180 mg/kg body wt.) i.p., for 24 h, showed a dose-independent increase in liver cytochrome P450 levels, together with an increase in lipid peroxidation, measured as production of thiobarbituric acid reactants. This oxidant condition elicited in the liver by DDT was not accompanied by any change in the activity of NADPH-cytochrome c reductase or in the rate of superoxide anion generation by liver microsomal fraction. The activities of superoxide dismutase and glutathione peroxidase were found to be increased in the higher dose DDT-treated rats, without any change in those from catalase and glutathione reductase. The results presented showed an oxidant condition in the liver elicited by DDT treatment of rats, without any adequate hypothesis proposed to explain these data.

Adrenochrome↗
PubMed1994

Influence of lindane and paraquat on oxidative stress-related parameters of erythrocytes in vitro.

1. The influence of lindane and paraquat on oxidative stress-related parameters of the red blood cell was studied in vitro. 2. Lindane addition did not modify either the t-butyl hydroperoxide-induced oxygen uptake of the erythrocytes and the induction time preceding it, or the activity of catalase, superoxide dismutase, glutathione peroxidase and glucose 6-phosphate dehydrogenase, in conditions of comparable levels of haemoglobin and methaemoglobin. 3. Red blood cells exposed to paraquat exhibited a concentration-dependent decrease in the t-butyl hydroperoxide-induced oxygen consumption and increments in either the induction period or in the activity of catalase and glucose 6-phosphate dehydrogenase, with no changes in superoxide dismutase activity and a small decrement in that of glutathione peroxidase. 4. These data indicate that lindane does not interfere with the oxidant status of the erythrocyte, while paraquat addition leads to an increment in the anti-oxidant capacity of the red blood cell.

Animals↗
PubMed1993

Differential effects of short-term lindane administration on parameters related to oxidative stress in rat liver and erythrocytes.

Parameters related to oxidative stress in rat liver and erythrocytes were studied after short-term administration (60 and 90 days) of 1000 ppm of lindane in the diet. Lindane induced an oxidative stress condition in the liver, which is related to an enhancement in microsomal NADPH-cytochrome c reductase and NADPH oxidase activities, superoxide radical formation and cytochrome P450 content, produced independently of the time of treatment. Also, decreased activities of glutathione peroxidase and catalase were concomitantly observed. Although these changes were paralleled by an increase in lipid peroxidation indices, such as production of thiobarbituric acid reactants and spontaneous chemiluminescence, no evidence of liver injury was obtained. Lindane treatment did not exert quantitatively important changes in the pro-oxidant/anti-oxidant status of the erythrocyte, with reduction in the red blood cell mass possibly reflecting actions of the insecticide on the erythropoietic process.

Animals↗
PubMed1993

Turnover of hepatic glutathione after acute lindane intoxication.

The administration of lindane (60 mg/kg) to fed rats diminished the content of hepatic glutathione (GSH) 4 h after treatment, which was recovered at 24 h. At these experimental times, the activities of glutathione peroxidase, glutathione reductase, glutathione-S-transferases and gamma-glutamyltransferase in the liver of lindane-treated rats and control animals were comparable. Liver GSH turnover, measured after a pulse of [35S]cysteine, was enhanced by 69% (P < 0.05) in lindane-treated rats 24 h after intoxication compared to controls, with a 63% (P < 0.05) increase in the estimated rate of GSH synthesis. It is concluded that lindane enhances GSH synthesis in rat liver 24 h after treatment as a consequence of the decrement in its content observed at early times of intoxication (4 h), thus allowing the recovery of the normal level of hepatic GSH.

Animals↗
PubMed1991

Liver lipid peroxidation-related parameters after short-term administration of hexachlorocyclohexane isomers to rats.

Rats treated with diets containing 20 ppm of alpha- or gamma-hexachlorocyclohexane (HCH) for 15 or 30 days showed increased levels of liver cytochrome P-450 followed by increased production of both thiobarbituric acid reactants by liver homogenates and microsomes and superoxide anion production by liver microsomes. In these animals superoxide dismutase (SOD) activity was also increased. In consequence, the ratio between SOD activity and microsomal superoxide radical (O2-.) production showed a slight increase after 15 days of treatment. However, after 30 days, there was a tendency for this ratio to decrease. Other parameters studied were liver glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione reductase and catalase (CAT) activities. Among them, only CAT activity showed a 26% and 38% increase after 15 or 30 days of treatment with the alpha-isomer. It is suggested that when lipid peroxidation is involved in the mechanism of toxicity of a xenobiotic, this parameter can be used to determine the no-observed-effect level.

Animals↗
PubMed1991

Effects of hyperthyroidism on rat liver glutathione metabolism: related enzymes' activities, efflux, and turnover.

The effect of hyperthyroidism on liver glutathione (GSH) metabolism was studied in fed rats after the administration of 0.1 mg T3/kg body wt, for 1-3 consecutive days. T3-calorigenesis resulted in elevated rates of O2 consumption by the liver, together with higher lipid peroxidative processes and GSH depletion, compared to the euthyroid state. The study of the enzymes related to GSH metabolism revealed no significant changes in the activity of glutathione peroxidase and glutathione reductase, with decreases (27-41%) in the activity of glutathione-S-transferases and marked elevation (133%) in that of gamma-glutamyl transferase, 3 days after T3 treatment. At this experimental time, the activity of the NADPH generating enzyme glucose-6-phosphate dehydrogenase was enhanced by 84% in the liver of T3-treated rats, compared to that in the controls. In these conditions, the canalicular efflux of GSH was not altered by T3, whereas net and fractional rates of sinusoidal GSH efflux were enhanced by 86% and 288%, respectively. The latter effect of hyperthyroidism was found in parallel with an enhancement in sinusoidal lactate dehydrogenase and protein release, suggesting that loss of GSH might be related to a permeabilization of the hepatocyte plasma membrane. Liver GSH turnover assessed after a pulse of [35S]cysteine resulted in a 209% increase in the fractional turnover rate in hyperthyroid rats over controls, under steady state conditions for both hepatic GSH pools, leading to a 62% enhancement in the respective turnover flux. Data suggest that the elevation in the sinusoidal GSH efflux from the liver and in the hepatic capacity to degrade the tripeptide are major mechanisms leading to GSH depletion in the liver of T3-treated rats. As the increased GSH use is not balanced by the elevation in GSH synthesis, a lower steady state level of GSH is attained in the liver.

Animals↗
PubMed1991

Mechanisms of lindane-induced hepatotoxicity: alterations of respiratory activity and sinusoidal glutathione efflux in the isolated perfused rat liver.

1. Lindane (25-60 mg/kg) at 24 h after dosage induced a dose-dependent increase in oxygen consumption by perfused rat livers, an effect not observed at early times (2-6 h) after administration. About 60% of the increase in liver oxygen uptake is suppressed by the antioxidant, desferrioxamine, indicating enhanced free radical activity induced by the insecticide. 2. The hepatic content of total GSH equivalents (GSH + 2GSSG) decreased 4 h after lindane treatment (60 mg/kg), together with significant diminution in net and fractional rates of sinusoidal GSH efflux, that returned to control values 24 h after treatment. 3. These data indicate that lindane resulted in marked changes in hepatic oxidative capacity and glutathione metabolism, which condition the production of oxidative stress in the liver at different times of intoxication.

Animals↗
PubMed1991

Effect of phenobarbital and 3-methylcholanthrene on the early oxidative stress component induced by lindane in rat liver.

1. Lindane administered to untreated rats or rats pretreated with phenobarbital (PB) or 3-methylcholanthrene (MC) increased liver lipid peroxidation, of the same magnitude in all groups. 2. PB pretreatment produced a 50% increase in lipid peroxidation (TBAR) by liver homogenates and microsomes, an effect accompanied by increases in cytochrome P-450, NADPH-cytochrome P-450 reductase, NADPH oxidase and microsomal superoxide anion production, MC pretreatment resulted in increases in liver cytochrome P-450 and NADPH oxidase only. 3. Pretreatment of rats with PB, but not MC or lindane, gave increases in glutathione peroxidase and reductase. 4. Pretreatment with PB, but not MC, increased liver GSH. Lindane decreased liver GSH to the same extent as PB plus lindane. 5. Biliary GSH, GSSG and bile flow were decreased by lindane to similar extents in all groups. 6. Lindane induced periportal necrosis with haemorrhagic foci in all groups. 7. Data presented indicate that the early lipid peroxidative response of liver to lindane was unchanged by PB- or MC-stimulated hepatic microsomal enzyme induction.

Animals↗
PubMed1990

Epithelial macrophages secrete a deactivating factor for superoxide release.

The release of superoxide anion (O2-) by inflammatory macrophages, multinucleated giant cells, and epithelioid cells, obtained by the insertion of round glass coverslips into the subcutaneous tissue of mice, was investigated. O2- was shown to be spontaneously released by cells on the surface of glass coverslips implanted up to 7 days, but not by cells obtained 14 or 21 days after coverslip implantation. The former showed increased O2- release when stimulated by phorbol myristate acetate, whereas cells harvested after 14 or 21 days implantation did not. The induction of delayed type hypersensitivity around coverslips implanted for 5 days increased spontaneous O2- release by these cells by 40%. On the other hand, when the same protocol was used with coverslips implanted for 14 days, O2- release was not detected. These results were viewed in regard to the composition of the cell population at each time point. When coverslips were removed after 14 days of implantation and the cells incubated for 30 minutes in vitro, the medium so conditioned inhibited O2- release by cells of 5 day old preparations. This indicates the release by cells on the longer term coverslips of a substance that inhibits O2- production by cells of coverslips implanted for 5 days only. This inhibitory activity could be suppressed by treating the conditioned medium with proteases. The factor was, however, heat stable and exerted its effects even when the test cells were exposed to phorbol myristate acetate.

Animals↗
PubMed1990

Lindane-induced liver oxidative stress.

The development of an oxidative stress condition in the liver by lindane intoxication is discussed as a possible hepatotoxic mechanism of the insecticide. Lindane is metabolized by liver microsomal enzymes to a variety of metabolites, which are susceptible of conjugation for proper elimination. In addition, the interaction of lindane with the liver tissue results in the induction of the microsomal cytochrome P-450 system, together with enhanced rates of superoxide radical generation and a significant increase in indicators of lipid peroxidation. Concomitantly, lindane intoxication induces a derangement of some antioxidant mechanisms of the liver cell, including decreased superoxide dismutase and catalase activities and alterations in reduced glutathione content leading to depressed GSH/GSSG ratios. The time course study of the changes in hepatic lipid peroxidation and antioxidant parameters are closely interrelated and coincide with the onset and progression of morphological lesions.

Animals↗
PubMed1990

Effect of dimethylsulfoxide on signal transduction in mutants of Saccharomyces cerevisiae.

1. As the first part of a study of pesticide toxicity we report the effects of the solvent dimethylsulfoxide (DMSO) on signal transduction in mutants of Saccharomyces cerevisiae. 2. The enzymes of trehalose metabolism, which are activated and deactivated by a "glucose signal" and by heat shock treatment, were chosen as targets for this study. 3. DMSO was shown to be able to permeate glucose and cAMP. The effects of glucose and cAMP were enhanced by pre-incubating the cells in the presence of DMSO. 4. No effects were observed during the heat shock, suggesting that the solvent acts on the cell membrane. 5. The results suggest that DMSO may be used as a vehicle for small molecules which do not easily penetrate yeast cell membranes, thus providing a new tool for biochemical and toxicological studies.

Cyclic AMP↗
PubMed1989

Lindane-induced liver oxidative stress: respiratory alterations and the effect of desferrioxamine in the isolated perfused rat liver.

The effects of lindane administration (25-60 mg kg-1 for 24 h) on hepatic oxygen consumption were studied in the isolated perfused rat liver, in the absence and presence of the iron-chelator free-radical scavenger desferrioxamine. Lindane elicits a dose-dependent enhancement of total oxygen uptake by the liver, which is largely inhibited by 0.55 mM desferrioxamine. Total desferrioxamine- sensitive oxygen consumption exhibits a maximal increase (213 per cent) at 60 mg of lindane kg-1 over control values and represents 21 per cent of the total oxygen consumption. At the different doses of lindane used, it was calculated that about 60 per cent of the total increase in oxygen uptake by the liver is accounted for by oxygen related to oxidative stress, probably utilized at different stages of the induced lipid peroxidative process.

Animals↗
PubMed1988

Liver and biliary levels of glutathione and thiobarbituric acid reactants after acute lindane intoxication.

The i.p. administration of 60 mg kg-1 body weight of lindane, the gamma-isomer of hexachlorocyclohexane, to fed rats led to an enhancement of hepatic lipid peroxidation after 24 h of treatment. This was evidenced by significant increases in the hepatic production and biliary release of thiobarbituric acid reactive substances, and in the biliary release of glutathione disulphide. Under these conditions, the content of cytochrome P450 was enhanced concomitantly with increases in the total microsomal oxygen uptake, superoxide radical generation and (+)-catechin (cyanid-3-ol) sensitive respiration. The glutathione status of hepatocytes was altered by lindane as the content and biliary release of glutathione disulphide was drastically augmented, leading to a decrease in the cellular and biliary GSH/GSSG ratios. It is suggested that lindane treatment leads to an induced oxidative capacity, which, in turn, alters the glutathione status of the liver tissue.

Animals↗
PubMed1988

Lindane-induced oxidative stress. I. Time course of changes in hepatic microsomal parameters, antioxidant enzymes, lipid peroxidative indices and morphological characteristics.

1. Lindane (60 mg/kg) administered orally to rats increased liver cytochrome P-450 content and superoxide radical (O2-.) generation 24 h after treatment, while formation of thiobarbituric acid reactants and NADPH/ADP-supported microsomal chemiluminescence were significantly increased 4 h after treatment. 2. Hepatic superoxide dismutase (SOD) and catalase decreased 6 h after lindane treatment and SOD/O2-. ratio progressively decreased during 4 to 24 h after lindane treatment. 3. Morphological evidence of hepatic cell injury after lindane treatment was seen at all times studied, and appeared to increase with time. 4. Lindane administration results in time-dependent oxidative stress in liver which involves an early component (4-6 h) related to the reductive metabolism of lindane, and a late component (24 h) associated with the induction of cytochrome P-450; the biochemical changes correlated with the observed morphological lesions.

Animals↗
PubMed1988

Lindane-induced oxidative stress. II. Time course of changes in hepatic glutathione status.

1. Four hours after treatment of rats with lindane (60 mg/kg), hepatic GSH content was decreased (22%) and GSSG was increased (20%), while biliary concentration and excretion of both GSH and GSSG and bile flow were diminished. These changes coincide with the onset of hepatic lipid peroxidation. 2. The changes induced by lindane at 4 h disappeared at 6 h after treatment, but liver GSSG content (91%), biliary GSSG excretion (133%) and bile flow (42%) were enhanced at 24 h. 3. The data indicate that lindane treatment elicits marked changes in hepatocyte glutathione status, with a decrease in the GSH/GSSG ratio at early (2-4 h) and late (24 h) periods of poisoning.

Animals↗
PubMed1986

Dose-dependent study of the effects of acute lindane administration on rat liver superoxide anion production, antioxidant enzyme activities and lipid peroxidation.

The administration of single i.p. doses of lindane (20, 40, 60 and 80 mg/kg) to rats produced a progressive increase in the liver microsomal content of cytochrome P-450 and in the rate of superoxide anion generation, as measured by adrenochrome formation. A dose-dependent increase in lipid peroxidation of liver homogenates, assessed by measuring thiobarbituric acid reactants, was also found. Lindane treatment did not alter the activity of liver glucose-6-phosphate dehydrogenase, glutathione reductase or glutathione peroxidase, while that of superoxide dismutase and catalase was significantly reduced. These changes were accompanied by a progressive liver steatosis. The collected metabolic data were interpreted in terms of a causal relationship between an increase in superoxide radical generation, secondary to cytochrome P-450 induction and a resulting increase in lipid peroxidation. The decrease in superoxide dismutase and catalase activities is likely to contribute to the increased levels of lipid peroxidation in view of their antioxidant properties.

Animals↗
PubMed1978

General effects of beryllium sulfate on isolated rat heart muscle mitochondrial fraction.

The effects caused by Be2+ on the properties of isolated rat heart muscle mitochondria were investigated. It has been shown that Be2+ enhances oxygen uptake by the mitochondrial fraction in the presence of oxidizable substrates. This is due to the uncoupling effect caused by Be2+ on the mitochondria, which also undergoes a swelling effect by this divalent ion that can be accounted by the retention of Be2+ by the mitochondria. The saturation of the organellae binding sites occurs when the concentration of the ion reaches a maximum of 6.2 mumoles/mg protein.

Adenosine Triphosphatases↗