摘要:

AbstractEffects of two classes of pyrethroids, permethrin and resmethrin (type I), cypermethrin and deltamethrin (type II), on basal (calmodulin‐deficient) and calmodulin stimulated activities of Ca2+ATPase and adenylate cyclase from rat brain were studiedin vitro. None of the pyrethroids inhibited synaptosomal basal Ca2+ATPase, but permethrin and deltamethrin inhibited basal adenylate cyclase in the nuclear fraction of a brain homogenate. Both groups of pyrethroids decreased the calmodulin activated Ca2+ATPase and adenylate cyclase from brain synaptosomes and nuclear fraction. The results indicate that calmodulin‐stimulated Ca2+ATPase is more sensitive to type II pyrethroids and pyrethroids are more effective on calmodulin stimulated enzymes than basal enzyme activities. Since calmodulin, adenylate cyclase and Ca2+ATPase are known to participate in various brain processes, it is possible that pyrethroids alter neural transmission, however, additionalin vivowork would be needed to confirm this possibil

ISSN:0260-437X    

DOI:10.1002/jat.2550070202

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractPregnant Sprague‐Dawley and Fisher 344 rats were treated on day 15 of gestation with Aroclor 1254 in a single dose ranging from 0 to 500 mg kg−1body weight and killed on day 18 of gestation. In the small groups of animals used for this study, no effect was observed on mean maternal liver or placental weight, or the number of fetal resorptions at any of the doses tested. Measurement of aryl hydrocabon hydroxylase (AHH) and 7‐ethoxycoumarin 0‐deethylase (7ECD) activity in tissue homogenates, however, showed that administration of Aroclor 1254 (15 mg kg−1body weight or greater) induced mono‐oxygenase activity in fetal liver. Both the AHH and 7ECD assay detected effects of PCBs with similar sensitivity, and the findings were comparable when homogenates were assayed instead of microsomes. These data were used to suggest technical approaches to the detection of mono‐oxygenase induction in placental tissue human populations ex

ISSN:0260-437X    

DOI:10.1002/jat.2550070203

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractSilicic acid and silicate dusts (slate dust and chrysotile asbestos) cause hemolysis of erythrocytesin vitro. The peroxidation of polyunsaturated fatty acids (PUFA) of erythrocyte membrane lipids is also enhanced by incubating the erythrocytes with silicic acid and silicate dusts inin vitro. Hemolysis of erythrocytes elicited by silicic acid and silicate dusts is inhibited significantly by polyvinyl‐pyrrolidone and dipalmitoyl lecithin (DPL). These agents, however, have no effect on silicic acid and silicate dust induced peroxidation of erythrocyte membrane lipids. On the other hand, peroxidation of erythrocyte membrane lipids, induced by silicic acid and silicate dusts, is inhibited almost completely by adding superoxide dismutase and catalase to the incubation system, whilst the hemolysis of erythrocytes induced by silicic acid and silicate dusts is unaffected by these agents. Similarly the lysis of erythrocytes, induced by silicic acid and silicate dusts, proceeds at a much faster rate than silicic acid and silicate dust induced lipid peroxidation. These results indicate that silicic acid and silicate dust induced hemolysis and lipid peroxidation represent two independent processe

ISSN:0260-437X    

DOI:10.1002/jat.2550070204

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractPreviously, Grahamet al.found evidence that pentobarbital‐induced sleeping time was enhanced in various animals following exposure to 1 ppm of ozone in air. The present study was undertaken to investigate whether similar ozone exposure would cause inhibition of metabolism of another model drug, [14C]antipyrine, in conscious rats. Furthermore, this study also investigated whether, like that of ozone, other lipid‐peroxidizing agents such as cadmium and carbon tetrachloride would affect metabolism of [14C]antipyrine in conscious rats.The results showed no significant effect of ozone exposure on subsequent metabolism of [14C]antipyrine in conscious rats as revealed by very similar14CO2exhalation rate (CER)‐time profiles before and after ozone treatment under various exposure protocols. Even though the exposure to ozone caused no inhibition of antipyrine metabolism in conscious rats, cadmium and carbon tetrachloride, on the other hand, markedly inhibited metabolism of this model drug. In agreement with the reported sex‐difference in toxic effects of cadmium, during the present study the cadmium‐induced inhibitory effect on the CER‐time profiles was observed in male but not in female rats. In contrast, no clear sex‐dependency was noted in the inhibitory effect of carbon tetrachloride on [14C]antipyri

ISSN:0260-437X    

DOI:10.1002/jat.2550070205

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractExperimental models for halothane hepatotoxicity require microsomal enzyme induction by phenobarbital or triiodo‐thyronine pretreatment and hypoxic conditions. The role of GSH in the metabolism of halothane, however, is still unclear. We therefore pretreated male rats with phorone to deplete hepatic GSH, phenobarbital as a microsomal enzyme inducer and exposed them to halothane 1 % for 4 h under hypoxia (10% O2). Increases in serum enzyme activities of alanine aminotransferase (GPT) and sorbitol dehydrogenase (SDH) were observed 24 and 48 h later. Histomorphological examinations showed centrilobular hepatic necrosis. In GSH‐depleted rats the increments of serum enzyme activities and histomrphological alterations were significantly aggravated as compared with controls.In this model (+)‐catechin protected against halothane‐induced hepatotoxicity as evidenced by reduced serum enzyme elevations and morphological alterations whereas diethyldithiocarbamate faiied to exert any protective effects. Free fluoride concentrations in plasma was used as an index of the non‐oxidative defluorination of halothane. Increased plasma fluoride levels were observed under conditions which evoked hepatotoxicity but did not correlate with the protective effect of (+)‐catechin. Our experimental data indicate that glutathione might be involved in the non‐oxidative metabolic pathways of halothane. Furthermore, (+)‐catechin seems capable of protecting against the direct toxic effect of halothane metabolites resulting from the red

ISSN:0260-437X    

DOI:10.1002/jat.2550070206

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe metabolism of dimethylarsinic acid (DMA) a common pesticide and the main metabolite of inorganic arsenic in mammals, has been studied in mice, hamsters and man. Mice and hamsters were administered a single dose of74As‐DMA (40 mg As/kg body weight) orally, while a human subject ingested DMA corresponding to 0.1 mg As/kg body weight. Ion exchange chromatography, paper electrophoresis, thin layer chromatography as well as arsine generation—gas chromatography combined with atomic absorption spectrophotometry or mass spectrometry were used to characterize the arsenic metabolites in urine and feces collected over 48 hours after treatment.In mice and hamsters 3.5% and 6.4% of the dose, respectively, were excreted in urine in the form of trimethylarsine oxide (TMAO). No TMAO was found in feces. A DMA‐complex was detected in urine and feces. It amounted to about 13% of the dose in mice and 15% in hamsters. About 80–85% of the dose was eliminated in urine and feces in the form of unmetabolized DMA. No demethylation of DMA to inorganic arsenic was observed. In man, about 4% of the dose was excreted in urine as TMAO and about 80%

ISSN:0260-437X    

DOI:10.1002/jat.2550070207

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThein vitroeffect of methylmercury (MM) on the enzymatic activities of brain cell specific marker enzymes, choline acetyltransferase (CAT), glutamic acid decarboxylase (GAD), 2′, 3′‐cyclic nucleotide phosphohydrolase (CNP), glutamine synthetase (GS) and enolase was examined. The results demonstrate that at 100 μM MM, GS activity was not affected whereas a small decrease in the activity of both GAD (20%) and enolase (10%) was observed. CNP and CAT activity appeared to be more sensitive toward MM with 100 μM MM producing inhibition of 50% and 30%, respectively. The addition of sulfhydryl protecting reagents such as DTT or sodium thioglycolate can restore the enzyme activities to normal control levels despite prior exposure of the enzyme

ISSN:0260-437X    

DOI:10.1002/jat.2550070208

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe mechanisms of toxicity to isolated rat hepatocytes of two structurally related naphthoquinones have been studied. Both 5‐OH‐1,4‐naphthoquinone (5‐OH‐1,4‐NQ; juglone) and 2‐OH‐1,4‐naphthoquinone (2‐OH‐1,4‐NQ; lawsone) caused a concentration‐dependent cytotoxicity to hepatocytes which was preceded by a depletion of intracellular glutathione. 5‐OH‐1,4‐NQ caused a depletion of intracellular glutathione when incubated either at 4°C or 37°C whereas 2‐OH‐1,4‐NQ caused a depletion of intracellular glutathione when the hepatocytes were incubated at 37°C but not at 4°C. 5‐OH‐1,4‐NQ but not 2‐OH‐1,4‐NQ reacted with glutathione in buffered solution. These results suggested that the depletion of intracellular glutathione by 2‐OH‐1,4‐NQ is enzyme mediated whereas in the case of 5‐OH‐1,4‐NQ the direct chemical reaction with glutathione may be largely responsible for the depletion. A critical role for depletion of protein thiols in menadione‐induced cytotoxicity has been proposed. In agreement with earlier work, menadione caused a decrease in protein sulphydryls prior to cell death, however, at cytotoxic concentrations of both 2‐OH‐1,4‐NQ and 5‐OH‐1,4‐NQ this decrease only accompanied rather than preceeded cell death.The mechanism of toxicity of 5‐OH‐1,4‐NQ is similar to that of other naphthoquinones and involves formation of its corresponding naphthosemiquinone, active oxygen species and redox cycling as it stimulated a disproportionate increase in both microsomal NADPH oxidation and oxygen consumption. No evidence for redox cycling of 2‐OH‐1,4‐NQ was obtained either with microsomes or hepatocytes and thus its cytotoxicity must involve a different mechanism to that currently proposed for other naphthoquinones. This inability of 2‐OH‐1,4‐NQ to redox cycle may be due to its very low one‐electron reduction potential (E1

ISSN:0260-437X    

DOI:10.1002/jat.2550070209

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractEffect of diazinon (10,20 and 40 mg/kg, i.p.) on the level of blood glucose in rats was investigated. Hyperglycaemia peaked 2 h after i.p. treatment with 40 mg/kg diazinon. The cerebral acetylcholinesterase activity was significantly reduced. The blood level of pyruvic acid was unchanged while that of lactic acid was significantly increased. Convulsions and biochemical changes caused by diazinon (40 mg/kg) were prevented by diazepam injected immediately after diazinon. In diazinon‐treated hyperglycaemic animals, the glycogen content of the brain was depleted, the activities of glycogen phosphorylase, phosphogiucomutase and hexokinase were significantly increased and the activity of glucose‐6‐phosphatase remained unchanged. Lactate dehydrogenase activity was also increased by treatment with diazinon. The induced changes may compensate for the energy requirement of stimulatory effects caused by dia

ISSN:0260-437X    

DOI:10.1002/jat.2550070210

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractFour groups of male and female Sprague‐Dawley rats were exposed for 13 weeks to 3,3‐dimethyl‐2‐butanol (PA) at concentrations of 0.00, 0.20, 1.00 or 5.00 mg/l (1 mg/l = 240 ppm). Exposures were for 6 hr per day, 5 days per week with sacrifices at 7 and 13 weeks of exposure, and at 4 weeks after exposure. The test animals were evaluated for abnormalities in physiology, behaviour, clinical laboratory parameters, and gross and microscopic morphology. No abnormalities were detected in electrocardiograms, respiratory indices, spontaneous activity, passive avoidance activity and open‐field behaviour. Clinical signs related to PA exposure included alopecia, ataxia and lacrimation. There were no biologically significant between‐group differences in body‐weights during the study. The clinical laboratory data demonstrated a 30% increase in serum cholesterol and bilirubin at 7 weeks in high‐dose males and an increase in urea nitrogen in intermediate and high‐dose males at 13 weeks. There were no abnormalities in hematologic or coagulation parameters. At necropsy there were no significant gross abnormalities; however, examination of organ weights revealed enlarged kidneys in high‐dose male rats at 13 weeks, enlarged ovaries in high‐dose female rats at 13 weeks, and microscopic study of tissue sections revealed minimal to mild renal tubular injury in high and possibly intermediate dose males at several sacrifices.These findings suggest that the primary target organ of PA, when given by inhalation, is the kidney in male rats and possibly the ovary in female rats. The renal changes in the high‐dose males were not fully reversible during the recovery period. Because abnormalities were also observed in the intermediate‐dose males, the no‐observed‐effect level is 0.2 mg/I. The renal lesions were morphologically similar to those reported in male rats exposed to hydrocarbons and may be unique to male rats. It must be emphasized that PA, like most alcohols, is not highly

ISSN:0260-437X    

DOI:10.1002/jat.2550070211

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY