A comparison of the effects of cyclosporine (CsA) on hepatic microsomal drug metabolism in three different strains of rat.
1. Male albino Wistar (W), Sprague-Dawley (SD) and Fischer-344 (F344) rats, Rattus norvegicus, were dosed orally once daily with cyclosporine (CsA), 25 mg/kg/day, for 14 days. Control and treated rats were then sacrificed and selected assays were performed to measure differences in hepatic microsomal enzyme activity including: protein (PROT), cytochrome P-450 (CYT-P450) and cytochrome b5 (CYT-b5) levels, NADPH-cytochrome c reductase (CYT-c) activity, ethylmorphine N-demethylase (ETM) and aniline hydroxylase (ANL) activities. 2. Two-way analysis of variance (ANOVA) indicated that the effect of treatment alone showed significant strain-related differences in all parameters examined except CYT-b5 levels, while the effect of strain alone indicated significant differences in PROT, CYT-B5, CYT-c, and ANL. 3. The interaction component of the two-way ANOVA (treatment x strain) indicated strain-related differences in substrate metabolism only (ETM and ANL). 4. F344 rats were found to be significantly different from either Sprague-Dawley or Wistar rats in terms of the effect of CsA on ETM and ANL metabolism.
Augustine
J A
JA
Department of Pharmacology-Physiology, School of Dental Medicine, University of Pittsburgh, PA 15261.
Zemaitis
M A
MA
D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D013045:Species Specificity
D003524:Cyclosporins; D011506:Proteins; D006899:Mixed Function Oxygenases