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 directly in cultured male Sprague-Dawley rat and OF-1 mouse hepatocyte monolayers. The activity of T(4)-UGT (pmol/min/g liver) in vitro in hepatocyte cultures 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 progressive decline in T(4)-UGT activity occurred over time in both rat and mouse hepatocyte cultures. Treatment of cultures with various model inducers such as phenobarbital (PB), beta-naphthoflavone (NF) and clofibric acid (CLO) induced a strong increase in T(4)-UGT activity in rat hepatocyte monolayers. In addition, and as expected from available in vivo data, treatment of rat hepatocyte cultures with NF also increased p-nitrophenol (PNP)-UGT activity and treatment with PB or CLO increased bilirubin (Bili)-UGT activity. In contrast, T(4)-UGT activity in mouse hepatocyte monolayers was not affected by the treatments, neither were PNP- and Bili- UGT activities. These in vitro data confirm our previous in vivo observations that these inducers increase rat but not mouse liver T(4)-UGT activities (Viollon-Abadie et al., 1999). The present study thus demonstrates that hepatocyte monolayers are appropriated for the evaluation and inter-species comparison of the effects of xenobiotics on T(4)-UGT activities.
Viollon-Abadie
C
C
Laboratoire de Biologie cellulaire, Faculté de Médecine et Pharmacie, place Saint-Jacques, 25030, Besançon, France.
Bigot-Lasserre
D
D
Nicod
L
L
Carmichael
N
N
Richert
L
L
D000818:Animals; D002478:Cells, Cultured; D002995:Clofibric Acid / Q000494:pharmacology; D004790:Enzyme Induction; D014453:Glucuronosyltransferase / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019324:beta-Naphthoflavone / Q000494:pharmacology; D000099237:UDP-Galactose Translocators; D000099148:UGT1A1 Enzyme
D002995:Clofibric Acid; D014453:Glucuronosyltransferase; D009004:Monosaccharide Transport Proteins; D010634:Phenobarbital; D019324:beta-Naphthoflavone; D000099237:UDP-Galactose Translocators; C499946:Ugt1a1 protein, rat; D000099148:UGT1A1 Enzyme; C117189:thyroxine-UDP-glucuronosyltransferase