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• W2098105917 abstract "Previous studies in vitro have revealed that L-754,394, an HIV protease inhibitor, is a potent suicide inhibitor of cytochrome P-450 enzymes. The present report examines the effect of chronic treatment of L-754,394 on hepatic cytochrome P-450s in adult male rats. L-754,394 was administered orally once a day for 7 days and resulted in significant changes in marker activities. An unusual parabolic (ascending, then descending) profile was observed for testosterone 2beta-/6beta-(CYP 3A1/2-catalyzed) hydroxylase activities during the 7-day treatment with 20 mg/kg L-754,394. These activities, which were elevated 2-fold on day 2, returned to basal levels by day 8. In contrast, testosterone 2alpha-/16alpha-(CYP2C11-catalyzed) hydroxylase activities showed an opposite parabolic (descending, then ascending) profile during the same period, reducing to 40% of control activities on day 4, followed by a rebounding trend. Immunoquantitation of CYP 3A1/2 and 2C11 showed that the expressed protein levels were in parallel with the associated activities. Furthermore, mRNA levels of CYP 3A2 and CYP2C11 showed the same trends as the protein expression of the respective isoforms. These observations show that L-754,394 perturbs the relative abundance of P-450 isoforms in rat liver by affecting the regulation at a pretranslational step. This may further involve a disturbance of hormonal homeostasis. Although serum levels of testosterone did not show a marked change during treatment, thyroxine and triiodothyronine markedly decreased on days 2 and 4, and subsequently increased to basal levels." @default.
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• W2098105917 date "1999-09-01" @default.
• W2098105917 modified "2023-09-23" @default.
• W2098105917 title "Modulation of rat cytochrome P-450 by an investigational HIV protease inhibitor." @default.
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