Effect of fumonisin B(1) on rat hepatic P450 system.
The effects of the mycotoxin fumonisin B(1) (FB(1)) on the hepatic cytochrome P450 system were investigated in male rats dosed daily by oral gavage with 3 mg FB(1) per kg body weight for 9 consecutive days. FB(1) 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 FB(1) 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 FB(1).
Spotti
M
Department of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Utrecht, P.O. Box 80152, 3508 TD, Utrecht, The Netherlands
Maas
RF
de Nijs CM
Fink-Gremmels
J