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Biomedical subjects

R C Schnell

Publications and source records attributed to R C Schnell.

At least 37 records · Page 2Linked to original sources
PubMed1984

Effect of acute and repeated chlordimeform treatment on rat hepatic microsomal drug metabolizing enzymes.

The effect of chlordimeform treatment on the hepatic microsomal drug metabolizing enzymes was examined in male and female rats following either acute or repeated treatment. After acute administration of chlordimeform (100 mg/kg, ip one hr prior to sacrifice) differential effects were observed in various parameters of the hepatic microsomal mixed function oxidase system with significant decreases in ethylmorphine metabolism, cytochrome P-450 content, NADPH cytochrome c reductase, and in the spectral binding of hexobarbital and aniline while no changes were found in the metabolism of aniline or p-nitroanisole. Durations of zoxazolamine-induced paralysis and pentobarbital-induced hypnosis were increased significantly after acute chlordimeform administration. Following repeated administration of chlordimeform (75 mg/kg ip for four days) to adult male rats, a decrease was observed in zoxazolamine-induced paralysis time while pentobarbital-induced hypnosis was not altered. Metabolism studies using isolated hepatic microsomal fractions showed a decrease rate of biotransformation of ethylmorphine and aniline while the activity of p-nitroanisole O-demethylase was not changed. No differences were found in cytochrome P-450 levels whereas microsomal spectral binding of hexobarbital was reduced while that of aniline was not affected. Following acute or repeated administration of chlordimeform to adult female rats, decreases in the hepatic microsomal metabolism of aniline, but not ethylmorphine or p-nitroanisole, were observed. Addition of chlordimeform to microsomal suspensions yielded a Type I spectral binding curve.

Amidines↗
PubMed1984

Effect of manganese on hepatic drug metabolism in male and female rats.

Experiments were conducted to examine the effect of manganese on drug response and metabolism in male and female rats. Three days after administration of manganese chloride (5 mg Mn/kg, ip), the duration of hexobarbital hypnosis was prolonged in male but not in female rats. Hepatic microsomal metabolism of aniline, ethylmorphine, and hexobarbital was significantly inhibited in male rats. Metabolism of aniline and ethylmorphine was also inhibited in female rats but to a lesser extent than in males. Hexobarbital metabolism was not inhibited in female rats. Cytochrome P-450 content was depressed only in male rats, while cytochrome b5 levels were decreased in both sexes. These results indicate that sex-related differences exist in the ability of manganese to alter drug response and metabolism.

Animals↗
PubMed1983

Circadian rhythm in acetaminophen toxicity: role of nonprotein sulfhydryls.

A circadian rhythm in the toxicity of acetaminophen administered at different times of the day was exhibited in male mice. Peak lethality (70% dead) occurred at 1800 hr and nadir lethality (10% dead) occurred at 1000 hr. Hepatic nonprotein sulfhydryl (NPS) concentrations also varied in a circadian manner and were found to exhibit an inverse relationship to the acetaminophen lethality rhythm, with the highest hepatic concentrations occurring at 1000 hr and the lowest concentrations occurring at 1800 hr. At 1800 hr when acetaminophen lethality was greatest and NPS levels the lowest, more reactive acetaminophen metabolites were found covalently bound to hepatic macromolecules as compared to those bound at 1000 hr when NPS levels were highest and acetaminophen lethality was lowest. Hepatic cytochrome P-450 levels measured at these two daily time periods did not differ. The plasma half-life of acetaminophen was significantly decreased at the 1000 hr time period as compared to the 1800 hr time period. These findings suggest that the normal daily changes in NPS levels may influence the lethality of acetaminophen.

Acetaminophen↗
PubMed1983

Effect of acute and repeated selenium treatment on hepatic monooxygenase enzyme activity in male rats.

The effect of sodium selenite administered acutely or repeatedly on the biochemical components of the hepatic microsomal monooxygenase enzyme system was examined in male rats. 72 h following acute administration of selenium (2.4 mg Se/kg, i.p.), there was a significant decrease in ethylmorphine-N-demethylase activity and cytochrome P-450 levels but no change in aniline hydroxylase or NADPH cytochrome c reductase activity. Following repeated administration of selenite in the drinking water (1, 2, or 4 ppm Se) for 30 days, there was no alteration in any of the parameters measured. Following the in vitro additions of selenite to microsomes obtained from untreated rats, ethylmorphine-N-demethylase and aniline hydroxylase activities were inhibited at selenium concentrations of 10(-4) M or greater, but the inhibition achieved was less than 50%. No alterations in cytochrome P-450 levels were observed. These results indicate that selenium is a rather weak, indirect, and substrate-specific inhibitor of the hepatic monooxygenase enzyme system.

Aniline Hydroxylase↗
PubMed1983

Effect of acute and repeated chlordimeform treatment on rat hepatic microsomal drug metabolizing enzymes.

The effect of chlordimeform (CDM) treatment on the hepatic microsomal drug metabolizing enzymes was examined in male and female rats following either acute or repeated treatment. After acute administration of chlordimeform (100 mg/kg, i.p., 1 hour before killing) differential effects were observed in various parameters of the hepatic microsomal mixed function oxidase system with significant decreases in ethylmorphine metabolism, cytochrome P-450 content, NADPH cytochrome c reductase, and in the spectral binding of hexobarbital and aniline while no changes were found in the metabolism of aniline or p-nitroanisole. Durations of zoxazolamine-induced paralysis and pentobarbital-induced hypnosis were increased significantly after acute CDM administration. Following repeated administration of CDM (75 mg/kg, i.p., for 4 days) to adult male rats, a decrease was observed in zoxazolamine-induced paralysis time while pentobarbital-induced hypnosis was not altered. Metabolism studies using isolated hepatic microsomal fractions showed a decreased rate of biotransformation of ethylmorphine and aniline while the activity of p-nitroanisole O-demethylase was not changed. No differences were found in cytochrome P-450 levels whereas microsomal spectral binding of hexobarbital was reduced while that of aniline was not affected. Following acute or repeated administration of CDM to adult female rats, decreases in the hepatic microsomal metabolism of aniline, but not ethylmorphine or p-nitroanisole, were observed. Addition of CDM to microsomal suspensions yielded a Type I binding curve.

Amidines↗
PubMed1983

Species and sex differences in selenium inhibition of hepatic drug metabolism in rodents.

Hepatic microsomal drug metabolism was assessed in male and female rats, mice and hamsters 72 hr after administration of sodium selenite. The greatest inhibitory effect of selenium on hepatic drug metabolism occurred in male rats where the magnitude of reduction in microsomal metabolism by selenium treatment of ethylmorphine and aminopyrine was disproportionately greater than the decrease in either cytochrome P-450 levels or metabolism of aniline. In contrast, the inhibition of metabolism of the three substrates in female mice and the decrease in ethylmorphine-N-demethylase in male mice were similar in magnitude to the reduction observed in cytochrome P-450 content. Hepatic microsomal metabolism in male and female hamsters was relatively resistant to the inhibitory effects of selenium. The inhibition of drug metabolism by selenium may reflect a specific effect of selenium on selected isozymes of cytochrome P-450.

Aminopyrine↗
PubMed1982

Cadmium inhibition of in vitro hepatic oxidative drug metabolism in the rat: comparison between ionic cadmium and cadmium-thionein.

The effectiveness of cadmium added in vitro in inhibiting the microsomal oxidative metabolism of ethylmorphine or aniline in rat hepatic microsomes was markedly decreased if the metal was added as cadmium-thionein when compared to ionic cadmium. These data are consistent with the hypothesis that cadmium thionein is less active biologically than ionic cadmium.

Aniline Hydroxylase↗
PubMed1981

Differential effects of cadmium on the hepatic microsomal cytochrome P-450 system in male and female rats.

Cadmium (Cd) produced a marked sex-related difference with respect to inhibition of the hepatic microsomal monooxygenase enzyme system in the rat. Following in vivo cadmium (2 mg/kg i.p.) treatment, significant decreases in the levels of cytochrome P-450, significant reductions in the magnitudes of spectral binding (aniline or ethylmorphine), and significant inhibitions of microsomal metabolism (aniline and ethylmorphine) were observed with microsomes isolated from male but not female rats. Of these parameters only aniline metabolism was significantly altered in females. Following the in vitro addition of Cd (10(-6) M to 10(-3) M) to hepatic microsomes isolated from untreated male or female rats, sex-related changes were also observed in these parameters. Significant, concentration-dependent reductions were observed in cytochrome P-450 levels of both sexes but the males showed greater sensitivity to the cadmium effect. With respect to binding spectra, cadmium addition produced a concentration dependent inhibition of aniline only in the male rat. Ethylmorphine binding was inhibited only at the higher cadmium concentrations in both sexes. With respect to drug metabolism, cadmium addition inhibited both aniline and ethylmorphine metabolism in male rats and only aniline metabolism in female rats. These results showed that there are sex-related differences in the interaction of the hepatic microsomal monooxygenase enzyme system with cadmium both after in vitro addition as well as in vivo treatment with the metal.

Animals↗
PubMed1981

Sex-related differences in selenium-induced alterations in drug action in the rat.

Three days after pretreatment of rats of both sexes with sodium selenite (2.4 mg Se/kg, ip) the duration of pentobarbital-induced hypnosis was potentiated in males but not females. Similar treatment with selenium led to a significant inhibition of ethylmorphine demethylase activity by hepatic microsomal enzymes obtained from male but not female rats. Selenium treatment did not alter the activity of aniline hydroxylase in animals of either sex. These data show that there is a sex-related difference in the ability of selenium to alter drug response and hepatic drug metabolism, which is substrate-specific, in the rat.

Aniline Hydroxylase↗
PubMed1981

Interaction between selenium and phenobarbital on drug response and hepatic microsomal enzyme activity in the male rat.

Pretreatment of male rats with phenobarbital markedly depressed the duration of pentobarbital hypnosis and stimulated the hepatic microsomal metabolism of ethylmorphine and aniline. Following selenium treatment there was a prolongation of pentobarbital hypnosis and an inhibition of metabolism of ethylmorphine with no effect on that of aniline. When phenobarbital and selenium were administered simultaneously, the opposing effects on the duration of pentobarbital hypnosis cancelled each other. With respect of hepatic metabolism, differential effects were observed with the inhibitory effect elicited by selenium on ethylmorphine metabolism being prevented by phenobarbital. However, selenium enhanced the stimulatory effect elicited by phenobarbital on aniline metabolism.

Aniline Compounds↗