ALTERED UDP-GLUCURONOSYLTRANSFERASE EXPRESSION IN NONALCOHOLIC STEATOHEPATITIS AND IMPLICATIONS FOR DRUG METABOLISM

Abstract

Nonalcoholic steatohepatitis (NASH) affects the regulation of drug metabolizing enzymes and transporters, which leads to a variability in the disposition of drugs for individuals. Previous studies have shown that UDP-glucuronosyltransferase (UGT) activity and expression can change over the progression of nonalcoholic fatty liver disease (NAFLD). This study examined the enzyme activity of the UGT1a9 isoform and the UGT2b cluster in NASH mice models. There was a significant upregulation in the protein expression of UGT1a9 and UGT2b, while the mRNA expression of UGT1a9 decreased significantly in the NASH mice. This data suggests that, while there may be posttranscriptional processing responsible for the contrast in mRNA and protein expression, NASH may alter the glucuronidation of compounds, especially therapeutic drugs. Future study should focus on how UGT regulation is changed in NASH patients to better predict drug exposure and adverse drug events.