IN VIVO INHIBITION OF BILIRUBIN CONJUGATION DOES NOT INDUCE A LOSS OF ITS PROTECTIVE EFFECT IN OXIDATIVE STRESS-INDUCED CHOLESTASIS

MARTÍN, PL; TAURIZANO, D; RAZORI, MV; ARRIAGA SMM; PISANI, GB; SANCHEZ POZZI EJ; ROMA, MG; BASIGLIO, CL

Rosario

Congreso; Reunión Anual 2019 Sociedad Argentina de Fisiología; 2019

Sociedad Argentina de Fisiología

Our group proved that induction of hemeoxygenase 1 (HO1) and consequent elevation of bilirubin (BR) protect the liver from oxidative injury occurring in cholestatic diseases. To assess whether BR thus generated needs to be conjugated to exert its protective effect, we aimed to impair BR conjugation by depleting the endogenous pool of UDP, cofactor of UDP-glucuronosyl transferase (UGT), key enzyme in BR conjugation. Male Wistar rats were used throughout. Oxidative cholestatic injury was induced by tert-butyl hydroperoxide (T, 440 μmol/kg b.w., i.p.). Induction of HO1 and inhibition of UGT were achieved by administration of hemin (H, 20 mg/kg b.w., i.p.) and galactosamine (G, 200 mg/kg b.w., i.p.), respectively. Results are expressed as media±SD. Bile flow (μl/min/g liver) decreased 4-6 h post T injection (1.65±0.73 vs 3.12±0.51 for control -T vehicle-, p