CYP2E1 and CYP3A1/2 gene expression is not associated with the ursodeoxycholate effect on ethanol-induced lipoperoxidation

Ethanol is a well-known hepatotoxicant inducing steatosis and membrane lipo peroxidation. The aim of the present study was to investigate in rats, whet her the protective effect of UDC on ethanol-induced lipid peroxidation may be related with CYP2E1 and CYP3A1/2 gene expression. We showed that UDC tre atment in ethanol-fed rats induced a significant decrease in liver triglyce ride concentration which was closely correlated with a reduction in malondi aldehyde and hydroxyalkenal levels. In chronically ethanol-fed rats, CYP2E1 and CYP3A1/2 gene expressions were increased by a post-transcriptional mec hanism. These inductions, mainly of CYP2E1, could take part in alcohol-indu ced hepatic lipoperoxidation. UDC modified neither the specific activity, n or the protein level, nor the mRNA level of CYP2E1 when compared with contr ol. UDC supplementation to alcohol diet did not prevent the increase in CYP 2E1 expression of ethanol-fed rats. Furthermore, CYP3A1/2 protein levels we re similarly increased by ethanol and ethanol plus UDC treatment. Therefore , UDC protective effect against ethanol-induced lipoperoxidation was not as sociated with a modification of CYP2E1 and CYP3A1/2 expression.