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R C Schnell

Publications and source records attributed to R C Schnell.

At least 55 records · Page 3Linked to original sources
PubMed1980

Sex-related differences in the effect of cadmium on the induction of hepatic microsomal monooxygenases by phenobarbital in male and female rats.

3 days following an intraperitoneal injection of cadmium [Cd] (2.0 mg Cd/kg) an inhibition in hepatic microsomal drug metabolism for ethylmorphine and aniline was observed in male rats. Such treatment in female rats only inhibited metabolism of aniline. Following treatment with phenobarbital (50 mg/kg, i.p., for 4 days), the metabolism of both substrates was induced in rats of both sexes. In male rats, but not in female rats, Cd blocked the inducing action of phenobarbital.

Animals↗
PubMed1980

Circadian rhythms in the biological response and disposition of ethanol in the mouse.

Circadian rhythms in the response to ethanol were investigated in male, Swiss-Webster mice. Significant circadian variations were observed in increased and decreased spontaneous locomotor activity induced by ethanol (2 or 4 mg/g i.p., respectively) and in the hypothermic response to ethanol with the greatest effect generally occurring during the dark phase of the 12 hr:12 hr. light-dark cycle when the normal activity of the animals was highest. Ethanol was also more lethal during the dark phases as compared to the light phase. Disposition studies showed that the in vivo rate of disappearance of ethanol from the blood and the in vitro metabolism of ethanol by hepatic alcohol dehydrogenase were invariant throughout the 24-hr period. Additional studies demonstrated that the duration of ethanol-induced hypnosis was longer and the concentration of ethanol in blood and brain tissue, at awakening, was lower during the dark phase as compared to the light phase. These data suggest that circadian rhythms observed in the pharmacological and toxicological effects of ethanol in mice do not result from daily fluctuations in drug disposition but are more likely subserved by temporal changes in the sensitivity of the central nervous system to ethanol.

Alcohol Oxidoreductases↗
PubMed1980

Cadmium-induced inhibition of zoxazolamine metabolism in male and female rats.

Pretreatment of rats with cadmium potentiates the duration of hexobarbital hypnosis and inhibits the rate of hepatic hexobarbital metabolism in male and female rats. In contrast, treatment with cadmium pe and female rats. Thus, sex-related differences in cadmium inhibition of hepatic drug metabolism is apparently substrate dependent.

Animals↗
PubMed1979

Dose-related alterations in growth and mineral disposition by chronic oral cadmium administration in the male rat.

The effect of cadmium (1, 10, or 100 ppm) administered to male rats in drinking water for 13 weeks on body weight and mineral disposition (Cd, Mg, P and Zn) in several body tissues was examined. Most alterations observed in these parameters occurred only at the 100 ppm dose of Cd. Terminal body weight was decreased by 10% in rats ingesting Cd at 100 ppm resulting from decreased food intake since weight gain/food consumption ratio was the same for all treatment groups. In serum, cadmium ingestion resulted in an inhibition of alkaline phosphatase activity at all concentrations and phosphorous was elevated only in animals receiving 100 ppm Cd. No changes were observed in Ca in urea. In bone, Cd decreased zinc content, increased Ca content, but did not influence bone ash, Mg or P and roentgenographic examination revealed no bone abnormalities. In both liver and kidney, cadmium ingestion did not influence intestinal absorption of Ca, Mg, P, or Zn or the renal excretion of Ca, P, or urea. The results of this study indicate that alterations in body weight and tissue mineral disposition resulting from chronic Cd ingestion are dose-related.

Alkaline Phosphatase↗
PubMed1979

Sex-related differences in biotransformation of aniline hydroxylase in Sprague-Dawley rats.

A significant difference was found in the rate of aromatic hydroxylation of the type II substrate, aniline, between male and female rats of the Sprague-Dawley strain. In addition, microsomal cytochrome P-450 levels were significantly lower in female rats and aniline-induced spectral binding was significantly greater in microsomes isolated from male rats. Castration caused a significant reduction in aniline metabolism in male rats and testosterone treatment elevated this metabolism toward control level. Treatment of male rats with 17beta-estradiol significantly reduced aniline hydroxylase activity and female rats receiving testosterone for 1 month exhibited significantly increased rates of aniline metabolism over control females. Enzyme activities measured in immature male and in mature and immature female rats were all significantly lower than in mature male rats. These results suggest that the metabolism of aniline in Sprague-Dawley derived rats is controlled by androgen and, thus, is sex-dependent.

Aniline Compounds↗
PubMed1979

Annual differences in daily variations in hepatic drug metabolizing enzyme activity and plasma hormone levels in the rat.

Daily variations in hepatic drug metabolism and in plasma corticosterone and insulin levels were examined at monthly intervals over the duration of 1 year. Annual differences were observed in the basal levels of all parameters. Consistent daily variations were observed only in plasma corticosterone levels, whereas daily variations in each of the other parameters occurred inconsistently over the year with significant variations being found in ethylmorphine metabolism and insulin levels only five times, and in aniline metabolism, six times. These data show that daily variations in the parameters examined do not occur in a regular manner.

Aniline Compounds↗
PubMed1979

Studies on cadmium-induced inhibition of hepatic microsomal drug biotransformation in the rat.

Cadmium is a potent inhibitor of hepatic microsomal drug biotransformation in the rat. Male rats receiving a single intraperitoneal dose of cadmium exhibit significant decreases in hepatic microsomal metabolism of a variety of substrates. The threshold cadmium dose is 0.84 mg Cd/kg, and the effect lasts at least 28 days. Mechanistically, the inhibitory effect results from decreased cytochrome P-450 content since cadmium does not alter NADPH cytochrome c reductase activity. This effect is also observed following acute oral administration of cadmium in doses greater than 80 mg Cd/kg but is not observed following chronic administration of the metal via drinking water in concentrations of 5-200 ppm for periods ranging from 2 to 50 weeks. A tolerance to the inhibitory cadmium effect is observed if male rats are pretreated with subthreshold doses of the metal prior to the challenge cadmium dose. The degree of tolerance can be overcome by increasing the challenge dose of cadmium. Characterization of the tolerance phenomenon in terms of onset, duration, and intensity reveals a good correlation with the kinetics of metallothionein production, suggesting that the underlying basis for the tolerance phenomenon is likely the induction of metallothionein. A sex-related difference in the inhibitory effect of cadmium was observed. Cadmium did not inhibit the metabolism of hexobarbital or ethylmorphine in female rats but did inhibit that of aniline or zoxazolamine. Cadmium did not lower cytochrome P-450 content in female rats.

Aniline Compounds↗
PubMed1978

Effect of acute and chronic cadmium treatment on hepatic drug metabolism in male rats.

The effect of acute and chronic cadmium administration on hepatic drug metabolism was investigated in the male rat. 3 days after the acute administration of cadmium by either the intraperitoneal (0.84 mg Cd/kg) or the oral (greater than 80 mg Cd/kg) route, there was a significant potentiation in duration of hexobarbital hypnosis and inhibition of hepatic microsomal metabolism of hexobarbital and aniline. Administration of cadmium in the drinking water at levels of 100 or 200 ppm Cd for periods of 2--12 weeks or at levels of 5 or 20 ppm Cd for 50 weeks did not produce alterations in either drug response or hepatitic drug metabolism. Significant levels of metallothionein, a cadmium binding protein, found in the liver of the rats receiving cadmium chronically may offer an explanation for the observed differences in drug metabolism between the acute and chronic administration of cadmium. In additional studies, pretreatment of the rats with subthreshold doses of cadmium (0.21 or 0.42 mg Cd/kg) intraperitoneally produced a tolerance to the alterations in drug metabolism induced by the previous cadmium dose (0.84 mg Cd/kg, i.p.). However, chronic cadmium treatment (5 or 20 ppm Cd for 50 weeks) did not impart any such tolerance to subsequently administered Cd (0.84 mg/kg) by the intraperitoneal route. The hepatic levels of metallothionein induced by the chronic cadmium treatment were only 30--60% of those induced by the subthreshold cadmium and thus may not have bound enough of the large challenge cadmium dose to produce the tolerance phenomenon.

Animals↗
PubMed1978

Zinc-induced protection against cadmium alteration of drug action.

Pretreatment of male rats with cadmium acetate potentiates the duration of hexobarbital hypnosis and inhibits the rate of hepatic microsomal drug metabolism. Pretreatment of rats with zinc acetate protects against these alterations in drug action elicited by cadmium.

Animals↗