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 well investigated. However, the data regarding the effect of alcohol on the regulation of UDP-glucuronosyltranferase (UGT) activity are less clear. The aim of the present study was to determine the role of alcohol in the regulation of UGT mRNA expression by using whole animal and primary cultured hepatocytes. Chronic ethanol feeding of rats significantly increased the expression of liver UGT1A1 mRNA to 177% of control. The mRNA levels for UGT1A5, UGT2B1 and UGT2B3 were also enhanced, but did not reach statistical significance. In cultured hepatocytes, treatment with either ethanol or isopentanol significantly increased the expression of UGT1A1, UGT1A5, UGT2B1, and UGT2B3 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 either ethanol or isopentanol. In conclusion, ethanol and isopentanol have direct roles in the regulation of UGT.