Effect of tauroursodeoxycholate and S-adenosyl-L-methionine on 17β-estradiol glucuronide-induced cholestasis

Background/Aims: S-adenosyl-L-methionine (SAMe) and tauroursodeoxycholate (TUDC) exert an additive ameliorating effect on taurolithocholate (TLC)-induced cholestasis, The aims were to investigate the protective effect of SAMe on 17beta-estradiol-glucuronide (17 beta EG) cholestasis and to find out whether SAMe and TUDC may exert an additive, ameliorating effect. Methods: Hepatocyte couplet function was assessed by canalicular vacuolar accumulation (cVA) of cholyllysylfluorescein (CLF), Cells were co-treated with 17 beta EG and SAMe, TUDC, or both (protection study), or treated with 17 beta EG and then with SAMe, TUDC or both (reversion study) before CLF uptake. Couplets were also co-treated with SAMe and dehydroepiandrosterone (DHEA), a competitive substrate for the sulfotransferase involved in 17 beta EG detoxification, The effects of 17 beta EG, SAMe and TUDC were also examined on intracellular distribution of F-actin. Results: Both SAMe and TUDC significantly protected against, and reversed, 17 beta EG-induced cholestasis, but their effects were not additive. DHEA abolished the protective effect of SAMe, 17 beta EG did not affect the uptake of CLF into hepatocytes at the concentrations used, and also, it did not affect the intracellular distribution of F-actin. Conclusions: 17 beta EG does not affect the uptake of CLF into hepatocytes, SAMe and TUDC protect and reverse 17 beta EG-induced cholestasis, but without an additive effect. Protection by SAMe may involve facilitating the sulfation of 17 beta EG. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B,V, All rights reserved.