Developmental levels and androgen responsiveness of hepatic mono-oxygenases of male rats perinatally exposed to maternally administered cimetidine

Bernard H. Shapiro, Milad Sami Bitar

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3 Citations (Scopus)

Abstract

Cimetidine, a widely prescribed, potent histamine Hz-receptor antagonist, is unrelatedly a mild antiandrogen. Since perinatal androgens are essential for normal masculine imprinting, we wanted to determine if maternally administered cimetidine interfered with the development of the male offspring's sex-dependent, hepatic drug-metabolizing enzymes. Cimetidine was administered in the mothers' drinking water at several levels reflecting both human and rat therapeutic-like doses from day 17 of gestation through day 7 of lactation. With the exception of a 30% decline in the Vmax. for hexobarbital hydroxylase during adulthood, the developmental profile ofmicrosomal drug-metabolizing enzymes, when measured at 1, 4 and 18 weeks of age, was generally unaffected by perinatal exposure to cimetidine. Furthermore, the levels of various components of the hepatic mono-oxygenase system (i.e. heme, cytochromes P-450 and b5, hexo-barbital hydroxylase and p-chloro-TV-methylaniline demethylase) following orchidectomy and androgen replacement at physiologic and inductive concentrations, were basically the same in control and cimetidine-exposed rats.

Original languageEnglish
Pages (from-to)85-98
Number of pages14
JournalToxicology Letters
Volume55
Issue number1
DOIs
Publication statusPublished - 1 Jan 1991

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Keywords

  • Cimetidine teratogenicity
  • Hepatic drug-metabolizing enzymes
  • Induction
  • Orchidectomy

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