Galactosamine (GAL) prevents ethinylestradiol (EE)-induced cholestasis

SANCHEZ POZZI, EJ; CROCENZI, FERNANDO A; PELLEGRINO, JOSÉ M; CATANIA, VIVIANA A; LUQUITA, MARCELO G

Salvador, Bahia

Congreso; Bianual Meeting of the IASL; 2004

Ethinylestradiol (EE) induces intrahepatic cholestasis in experimental animals, being its derivative ethinylestradiol 17ß-glucuronide a presumed mediator of this effect. To test whether glucuronidation is a relevant step in the pathogenesis of cholestasis induced by EE (5 mg/Kg bw, s.c., for 5 consecutive days), the effect of simultaneous administration of galactosamine (200 mg/kg bw, i.p.) on biliary secretory function was studied. A single injection of the same dose of galactosamine was able to decrease hepatic UDP-GA levels by 85% and excretion of EE-17ß-glucuronide after administration of a tracer dose of [3H]EE by 40%. When administered for 5 days, galactosamine itself did not alter any of the serum markers of liver injury studied (AST, ALT, ALP) or biliary secretory function. When coadministered with EE, galactosamine partially prevented the impairment induced by this estrogen in total bile flow, the bile salt independent fraction of bile flow, basal bile salt secretion and the secretory rate maximum of tauroursodeoxycholate. In conclusion, galactosamine administration partially prevented EE-induced cholestasis by a mechanism involving decreased UDP-GA availability for subsequent formation of EE 17ß-glucuronide. The evidence thus supports the hypothesis that EE 17ß-glucuronide is involved in the pathogenesis of EE cholestasis.