Effect of fumonisin B1 on rat hepatic P450 system

Department of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Utrecht, P.O. Box 80152, 3508 TD Utrecht, The Netherlands; TNO Nutrition and Food Research Institute, P.O. Box 360, 3700 AJ Zeist, The Netherlands
03/2000; DOI: 10.1016/S1382-6689(00)00040-5
Source: OAI

ABSTRACT The effects of the mycotoxin fumonisin B1 (FB1) on the hepatic cytochrome P450 system were investigated in male rats dosed daily by oral gavage with 3 mg FB1 per kg body weight for 9 consecutive days. FB1 treatment resulted in a reduced weight gain. At the same time, CYP2E activity was increased, which is considered to mark the metabolic changes inherent to growth retardation in young rats. Treatment with FB1 also resulted in a selective inhibition of CYP2C11 and to a lesser extent, CYP1A2 in liver microsomes obtained from treated animals, whereas it did not affect significantly the activity of CYP2A1/2A2, CYP2B1/2B2, CYP3A1/3A2 and CYP4A. The significant inhibition of CYP2C11 is considered to reflect a suppressed activity of protein kinase activity resulting from the inhibition of sphingolipid biosynthesis caused by FB1.

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