Physiological concentrations of unconjugated bilirubin (UB) prevent oxidative stress (OS)-induced cholestasis in the isolated and perfused rat liver (IPRL)

BASIGLIO CL; TOLEDO FD; BOAGLIO AC; ARRIAGA SM; OCHOA JE; SANCHEZ POZZI EJ; MOTTINO AD; ROMA MG

Buenos Aires

Congreso; VIII International Congress of the SFRBM - South American Group; 2013

Society for Free Radical Biology and Medicine (SFRBM)

We previously showed in isolated rat hepatocyte couplets that OS induces secretory failure by endocytic internalization of canalicular transporters (Bsep and Mrp2), as a consequence of actin cytoskeleton disarrangement. Bilirubin is an endogenous antioxidant, but its role in the prevention of OS-induced cholestasis is uncertain. Here, we evaluated the capacity of UB to limit the alterations in biliary secretory function, using tert-butilhydroperoxide (tBuOOH) in the IPRL model. tBuOOH (75 µM) induced an abrupt increase in the oxidized glutathione-to-total glutathione ratio in bile (+167±28%) and pre-perfusion with UB (17 µM) prevented this phenomenon (p