Endothelin 3 (ET-3) prevents estrogen-induced colestasis in the rat.

MYRIAN R. RODRIGUEZ; MANUELA MARTINEFSKI; VALERIA TRIPODI; MARCELO S. VATTA; LILIANA G. BIANCIOTTI

Foz de Iguazu

Congreso; First Panamerican Congress of Physiological Sciences.; 2014

Endothelin 3 (ET3) prevents estrogen-induced cholestasis in the rat. Rodriguez MR1, Martinefski M3, Tripodi V3, Vatta MS2, Bianciotti LG1,2. In previous studies we reported that ET3 induces choleresis through ETB receptors coupled to nitric oxide. ET3 enhances both bile acid dependent and independent bile flow independently of hemodynamic changes and promotes the translocation to the plasma membrane of the main hepatic transporters involved in bile genesis and increases their mRNA expression. Therefore we aimed to establish whether ET3 played a beneficial role in hepatocellular cholestasis. Sprague-Dawley rats were infused with ET3 or vehicle for 30 min followed by estradiol 17B-d-glucuronide (E217G) administration to induce cholestasis. Bile samples were collected every 5 min for 120 min. Bile flow was calculated and cholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, lithocholic acid in their free, glycine and taurine derivative forms were assessed in bile samples by capillary electrophoresis. Infusion of ET3 enhanced bile flow through ETB receptors. However ET3-induced choleresis was not modified by the administration of E217G. Furthermore ET3 also modified the profile of bile acids as compared with control and E217G. Present findings show that ET3 through ETB receptors prevents estrogen-induced cholestasis in the rat and modifies the bile acid profile excretion. Results further suggest that the ETB receptor may represent a promising therapeutic target in pathophysiological situations like hepatocellular cholestasis.