Objective: To investigate whether ethanol and isopentanol could modulate the drug metabolism by regulating uridine diphosphate glucuronosyltransferase (UGT) expression in rat livers and cultured rat hepatocytes.
Methods: Rat livers and primary rat hepatocyte cultures have been used to determine the mRNA levels of five UGT isoenzymes following treatment with ethanol and isopentanol.
Results: Following treatment with alcohol in rats, UGT1A1 mRNA and UGT1A5 mRNA were increased to a mean of 177% and 166% of control, respectively. The mRNA levels of UGT2B1 and UGT2B3 were also increased in alcohol-treated rats to 178% and 132% of control, respectively. Incubation of hepatocytes with ethanol and isopentanol significantly increased the mRNA expression of UGT1A1, UGT1A5, UGT2B1 and UGT2B3 mRNA.
Conclusions: The expression of UGT can be regulated by ethanol and isopentanol. As a result, chronic alcohol consumption may modify the metabolism of numerous endogenous and exogenous compounds, in particular some drugs, which are substrates of these UGT isoenzymes.