Alcohol up-regulates UDP-glucuronosyltransferase mRNA expression in rat liver and in primary rat hepatocyte culture

The interactions between alcohol and cytochrome P-450 enzymes have been wel l investigated. However, the data regarding the effect of alcohol on the:re gulation of UDP-glucuronosyltranferase (UGT) activity are less clear. The a im of the present Study was to determine the role of alcohol in the regulat ion of UGT mRNA expression by using whole animal and primary cultured hepat ocytes. Chronic ethanol feeding of rats significantly increased the express ion of liver UGT1A1 mRNA to 177% of control. The mRNA levels for UGT1A5, UG T2B1 and UCT2B3 were also enhanced, but did not reach statistical significa nce. In cultured hepatocytes, treatment with either ethanol or isopentanol significantly increased the expression of UGT1A1, UGT1A5, UGT2B1, and UGT2B 3 mRNAs, but to different degrees. The induction of UGT1A1 and UGT2B1 mRNAs by ethanol or isopentanol was time-dependent and maximal changes occurred at 48 h. The expression of UGT1A6 mRNA was not significantly modified by ei ther ethanol or isopentanol. In conclusion, ethanol and isopentanol have di rect roles in the regulation of UGT.