Changes in the amounts of cytochromes P450 in rat hepatic microsomes produced by cyclosporin A.
1. The effect of cyclosporin A, an immunosuppressive drug, on the levels of individual cytochromes P450 of rat liver was studied by immunoblotting with specific antibodies. Changes in the metabolic activities of the microsomal enzymes were similarly studied. 2. Total P450 was decreased by treatment with cyclosporin A for 17 days. NADPH-P450 reductase activity was also decreased by treatment with cyclosporin A for 10 days and decreased further after 17 days. 3. Cytochromes 2B2 and 2C6 concentrations were decreased by treatment with cyclosporin A for 17 and 10 days, respectively. Administration of cyclosporin A for 17 days also decreased the levels of the male specific cytochromes 2C11 and 3A2, and consequently decreased testosterone 2 alpha-, 16 alpha-, 2 beta- and 6 beta-hydroxylation activities. Shorter periods (7 and 10 days) of cyclosporin A treatment decreased the level of cytochrome 3A2, which metabolizes cyclosporin A. In contrast, the level of cytochrome 2C13 was unchanged.
Isogai
M
M
Daiichi Pure Chemicals Co., Ltd. Tokai Research Laboratories, Ibaraki, Japan.
Shimada
N
N
Kamataki
T
T
Imaoka
S
S
Funae
Y
Y
D000818:Animals; D000918:Antibody Specificity; D016572:Cyclosporine / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism*; D006900:Hydroxylation; D015151:Immunoblotting; D007527:Isoenzymes / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone
D007527:Isoenzymes; D013739:Testosterone; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases