DEXAMETHASONE PROTECTION IN A MICE ESTROGEN-INDUCED CHOLESTASIS MODEL

FAZZI, AGUSTINA; HILLOTE, GERALDINE L; SALAS, GIMENA; MASSA, ESTEFANIA; FRANCÉS, DANIEL EA; SANCHEZ POZZI, ENRIQUE J.

Buenos Aires

Congreso; Reunión Anual SAFIS 2023; 2023

Sociedad Argentina de Fisiología

Introduction. Estrogen-induced cholestasis is a common pathology in susceptible pregnant women. A murine model of this pathology consists in a 5-days administration of 17-ethinylestradiol (EE) to rats or mice. EE administration reduces bile flow and bile salt synthesis by altering transporters and enzymes responsible for maintaining the normal bile salt excretion. Cholestatic murine models have exhibited substantial infiltration of innate immune cells and elevated levels of proinflammatory cytokines such as TNFα and IL-1β in the liver. These cytokines can exacerbate the cholestatic effects triggered by estrogens. This study proposes the use of Dexamethasone (Dex) due to its potent anti-inflammatory properties. Aim. To evaluate whether the administration of Dex in a mice EE-induced cholestasis model improves bile flow, bilirubin biliary excretion rate (ER) and plasma levels of liver markers enzymes. Methods. Male C57BL/6 mice were randomly divided into four groups: (a) Control (vehicles); (b) EE (10 mg/kg/day, s.c., 5 days); (c) Dex (1 mg/kg/day, i.p. 5 days); and (d) EE+Dex. The common bile duct was catheterized via a trans duodenal surgery and bile was collected for 30 min. Plasma samples were used to measure the enzymes: Alkaline Phosphatase (ALP), Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST). Also, the concentration of bilirubin was determined in bile samples. Results. (Mean±SEM. n=6. * p