Inhibition of drug metabolizing enzymes in the rat after Bacillus Calmette Guerin treatment

D. Farquhar, T. L. Loo, J. U. Gutterman, Evan M Hersh, M. A. Luna

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Drug metabolizing enzyme activities and protein content of hepatic microsomal preparations from adult Sprague Dawley rats were examined at 3,6,10 and 14 days after intravenous, subcutaneous and intradermal administration of two different strains of Bacillus Calmette Guerin (BCG). Pasteur liquid strain BCG, injected intravenously at 6 x 108 organisms/m2 in normal saline, caused 20-45 percent reduction of aniline hydroxylase (AH) and 5 (3,3 dimethyl 1 triazeno)imidazole 4 carboxamide demethylase (DICD) activities and the cytochrome P 450 content of microsomes from female rats but only 10-25 percent decrease in these parameters in males. Microsomal protein content was decreased 30-40 percent in both sexes on days 10-14. Administration of BCG by the subcutaneous route caused only 5-25 percent impairment of AH and DICD activities in female rats, while intradermal administration of the adjuvant was without discernible effect on the rat hepatic microsomal drug metabolizing system. The duration of pentobarbital induced narcosis was increased up to 70 percent in both male and female rats after intravenous administration of BCG. Tice strain lyophilized BCG at the same dose elicited similar but lesser effects. BCG added in vitro had no effect on AH and DICD activities. Livers of rats treated intravenously contained numerous granulomatous lesions throughout the parenchyma; the damage was variable and less severe in the subcutaneously treated animals. Intradermally treated rats showed normal liver histology.

Original languageEnglish (US)
Pages (from-to)1529-1535
Number of pages7
JournalBiochemical Pharmacology
Volume25
Issue number13
DOIs
StatePublished - 1976
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology

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