ANTICHOLESTATIC MECHANISMS OF OBETICHOLIC ACID (OCA) IN LIPOPLYSACARIDE (LPS)-INDUCED CHOLESTASIS IN THE RAT

RAZORI, MARÍA V; MARTÍN, PAMELA; BAROSSO, ISMAEL R.; MEDEOT, ANABELA; CIRIACI, NADIA; ANDERMATTEN, ROMINA B.; SCHUCK, VIRGINIA; SALAS, GIMENA; BASIGLIO, CECILIA L; RUIZ, MARÍA LAURA; ROMA, MARCELO G

Ciudad de Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2021

Sociedad Argentina de Investigación Clínica

Sepsis-induced cholestasis is due the release of inflammatory cytokines induced by LPS from Gram (-) bacteria, which impair expression/ localization of hepatocellular transporters. There is no therapyfor this condition. OCA is a potent FXR agonist used to treat human inflammatory chronic cholestasis. We ascertained here its anticholestatic mechanisms in LPS-induced cholestasis.Methods: Male Wistar rats were randomized in Control, OCA (20 mg/Kg/day, i.p., 6 days), LPS (6.5 mg/Kg, i.p., last 2 days) and OCA+ LPS groups. Then, we assessed serum alkaline phosphatase(ALP), a surrogate of bile salt (BS) hepatic accumulation, and taurocholate- stimulated BS output (BSO). mRNA/protein levels of Bsep and Mrp3 (apical and sinusoidal BS efflux pumps, respectively) and Ntcp (BS uptake carrier) were assessed by either or both Real time PCR and Western blot. Bsep localization was assessed by immunohistochemistry followed by confocal microscopy and image analysis. The inflammatory cytokines TNF-α and IL-1β were measured in serum by ELISA.Results: (*p