ADENOVIRUS-MEDIATED HUMAN AQUAPORIN-1 EXPRESSION IN HEPATOCYTES IMPROVES LIPOPOLYSACCHARIDE-INDUCED CHOLESTASIS

DANIELLI MAURO; MARRONE, JULIETA; MARINELLI RA; GASPARI CESAR

Buenos Aires

Congreso; Congreso Sociedades Biociencias; 2017

Sociedad Argentina de Fisiología (SAFIS) y otras

Lipopolysaccharides (LPS) are known to cause cholestasisin sepsis. There is evidence that a defective expressionof canalicular aquaporin water channels contributesto bile secretory failure in LPS-induced cholestasis.Thus, we studied whether the hepatic adenovirus-mediatedtransfer of human aquaporin-1 gene (haqp1) canimprove the cholestasis induced by LPS. Adenoviralvector encoding hAQP1 (AdhAQP1) or control vectorwas administered to rats by retrograde intrabiliary infusion.Hepatocyte canalicular hAQP1 expression was assessedby liver immunostaining and immunoblotting inpurified plasma membranes.LPS significantly reducedbile flow and biliary bile salt (BS) excretion by 30%and 45%, respectively. AdhAQP1-treatment normalizedboth bile flow and biliary BS excretion in LPS-inducedcholestasis. Moreover, markedly elevated serum BSlevels in cholestatic rats, were almost restored with theAdhAQP1 hepatic transduction (control(C):34±4;C+AdhAQP1:29±6;LPS:114±11*;LPS+AdhAQP1:58±12μM; *P