EurekaMag.com logo
+ Site Statistics
References:
53,214,146
Abstracts:
29,074,682
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Effects of methapyrilene hydro chloride on hepato carcinogenicity and pento barbital induced sleeping time in rats and mice


Toxicology & Applied Pharmacology 66(2): 252-258
Effects of methapyrilene hydro chloride on hepato carcinogenicity and pento barbital induced sleeping time in rats and mice
In a 6-8-mo. dose-response toxicity study, methapyrilene hydrochloride (HCl) was administered in the feed to Fischer-344/N rats and B6C3F1 mice at concentrations of 125, 250, 500, 1000, or 2000 ppm. After 26 wk, rats fed the higher dose levels of methapyrilene HCl developed cholangiocellular carcinomas in addition to severe hepatotoxic lesions. After 31 wk, mice exhibited only mild hepatotoxicity from ingesting methapyrilene HCl, even at the higher dose levels. The duration of sodium pentobarbital-induced sleeping time (PEN-induced ST) is determined by the rate of hepatic metabolism of PEN and can therefore be used as an in vivo measurement of the level of hepatic detoxifying enzymes. A subsequent study was undertaken with PEN-induced ST to investigate differences in the effect of methapyrilene HCl on hepatic detoxifying enzymes between the 2 species; in this study, prior treatment with methapyrilene HCl significantly increased PEN-induced ST of rats but not of mice, indicating that methapyrilene HCl had a suppressive effect on detoxifying enzymes in rats but not in mice. In other groups in this study, phenobarbital, a known inducer of hepatic detoxification enzymes, was administered simultaneously with methapyrilene HCl to both rats and mice. Methapyrilene HCl plus phenobarbital exerted a synergistic effect of enzyme induction in mice. In rats, the phenobarbital-induced hepatic enzymes increased the rate of hepatic detoxification of methapyrifene HCl, as measured by a reduction of PEN-induced ST as compared with that in control rats or rats receiving methapyrilene HCl alone. The difference in the effects of methapyrilene HCl on hepatic detoxifying mechanisms of rats and mice, as indicated by the metabolism of PEN, may explain the difference between the 2 species in their susceptibility to the hepatocarcinogenic effects of methapyrilene HCl.

(PDF 0-2 workdays service: $29.90)

Accession: 005314037



Related references

Different effects of delta 9 tetra hydro cannabinol and cannabidiol by 3 routes of administration on pento barbital induced sleeping time in mice. Research Communications in Substances of Abuse 2(3): 213-220, 1981

Sex differences in the effects of delta 9 tetra hydro cannabinol and cannabidiol on pento barbital induced sleeping time and hepatic microsomal drug metabolizing enzyme systems in mice. Yakugaku Zasshi 103(12): 1289-1297, 1983

Correlation of pheno barbital induced and skf 525 a 2 di ethylaminoethyl 2 2 diphenyl valerate hydro chloride induced modification of pento barbital hypnosis with alteration of in vivo and in vitro pento barbital metabolism in the rat. Pharmacology (Basel) 16(4): 181-192, 1978

Influence of ozone on pento barbital induced sleeping time in mice rats and hamsters. Toxicology & Applied Pharmacology 61(1): 64-73, 1981

Effects of chronic heat and restriction stress on thio pental pento barbital and barbital activity in the rat pento barbital and barbital activity in the rat abstract sleeping time/. Federation Proceedings 28(2): 675, 1969

Extrapulmonary effects of nitrogen di oxide as reflected by pento barbital induced sleeping time in mice. Toxicology Letters (Shannon) 6(4-5): 267-274, 1980

Effect of oxamniquine on pento barbital induced sleeping time in rats. Pharmacological Research Communications 12(6): 549-556, 1980

The effects of methapyrilene hydrochloride on hepatocarcinogenicity and pentobarbital-induced sleeping time in rats and mice. Toxicology and Applied Pharmacology 66(2): 252-258, 1982

Comparison of the effects of acute and subchronic administration of aroclor 1254 a commercial mixture of poly chlorinated bi phenyls on pento barbital induced sleep time and carbon 14 labeled pento barbital disposition in mice. Journal of Toxicology & Environmental Health 11(4-6): 917-932, 1983

Circadian control of the development of tolerance to pento barbital induced sleeping time in rats. Federation Proceedings 43(4): ABSTRACT 3878, 1984