Induction of microsomal epoxide hydrolase by tienilic acid in the rat

The effects of tienilic acid [2,3-dichloro-4-(2-thienylcarbonyl)phenoxy acetic acid] on drug-metabolizing enzymes in the rat liver and kidneys were studied. Short-term treatment for 2 weeks (450 mg per kg per day) increased the activity of microsomal epoxide hydrolase at least two-fold in both rat liver and kidneys. The effect of tienilic acid on the activity of microsomal epoxide hydrolase in the rat liver correlated with the dose at levels of 20-450 mg per kg per day for 14 days (r = 0.92). Tienilic acid had only marginal effects on cytochrome-P-450-mediated mono-oxygenases. Tienilic acid caused an approximately two-fold increase in glucuronide conjugation of 4-methylumbelliferone in the liver. No increase in the activity of rat hepatic microsomal UDP-glucuronosyltransferase toward O-aminophenol was detected. According to these results, tienilic acid can be regarded as one of the most specific inducers of microsomal epoxide hydrolase.