[Effect of bemethyl on cytochrome P-450-dependent monoxygenases in the human liver and lymphocytes].
Effects of the actoprotector bemithyl (50 mg/kg, p.o.) upon a single or five-fold administration on the cytochrome P-450 and b5 content and the isoform-specific and nonspecific monooxygenase activity [aminopyrine-N-demethylase, aniline-p-hydroxylase, 4-nitroanisole-o-demethylase,2,5-diphenyloxazole-p-hydroxylase, 7-ethoxyresorufin-o-deethylase (EROD), benzyloxyresorufin-o-debenzylase (BROD)] in rat liver were evaluated. In addition, the influence of bemithyl (0.(1)-100 microM) on the development of EROD and BROD activity was studied on the mitogen-stimulated human lymphocytes in vitro. Administered in rats, bemithyl exhibited the properties of a cytochrome P-450 inductor of the mixed type, which was manifested by an increase in the total cytochrome P-450 content in liver microsomes and in the monooxygenase activity related to both Ah-receptor-dependent and -independent isoforms (except for the aniline-p-hydroxylase activity). The induction of the monooxygenase activity realized by Ah-receptor-dependent isoforms (4-nitroanisole-o-demethylase, 2,5-diphenyloxazole-p-hydroxylase, and EROD activity) was more pronounced, reaching maximum upon a single drug administration. Acting upon the human lymphocytes in vitro, high concentrations of bemithyl increased expression of the EROD activity, while low drug concentrations stimulated the BROD activity.
Sorokina
E A
EA
Clinical Immunology and Immunopharmacology Department, All-Russia Center for Ophthalmic and Plastic Surgery, ul. Kol'tsevaya 47, Ufa, Bashkortostan, 450040 Russia.
Sibiriak
S V
SV
Sergeeva
S A
SA
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats
D001562:Benzimidazoles; D007527:Isoenzymes; C049825:bemethyl; D003577:Cytochrome P-450 Enzyme System