Effects of model inducers on thyroxine UDP-glucuronosyl-transferase activity in vitro in rat and mouse hepatocyte cultures

Thyroxine (T-4)-UDP-glucuronosyltransferase (UGT) activity was measured dir ectly in cultured male Sprague-Dawley rat and OF-1 mouse hepatocyte monolay ers. The activity of T-4-UGT (pmol/min/g liver) in vitro in hepatocyte cult ures was, after 24 hr in culture, equivalent to that previously measured in vivo in rat and mouse liver microsomes (Viollon-Abadie et al., 1999). A pr ogressive decline in T-4-UGT activity occurred over time in both rat and mo use hepatocyte cultures. Treatment of cultures with various model inducers such as phenobarbital (PB), beta -naphthoflavone (NF) and clofibric acid (C LO) induced a strong increase in T-4-UGT activity in rat hepatocyte monolay ers, In addition, and as expected from available in vivo data, treatment of rat hepatocyte cultures with NF also increased p-nitrophenol (PNP)-UGT act ivity and treatment with PB or CLO increased bilirubin (Bili)-UGT activity, In contrast, T-4-UGT activity in mouse hepatocyte monolayers was not affec ted by the treatments, neither were PNP- and Bili- UGT activities. These in vitro data confirm our previous in sire observations that these inducers i ncrease rat but not mouse liver T-4-UGT activities (Viollon-Abadie et al., 1999), The present study thus demonstrates that hepatocyte monolayers are a ppropriated for the evaluation and inter-species comparison of the effects of xenobiotics on T-4-UGT activities. (C) 2000 Elsevier Science Ltd. All ri ghts reserved.