Nitric oxide suppression reversibly attenuates mitochondrial dysfunction and cholestasis in endotoxemic rat liver

摘要: This study aimed to examine whether nitric oxide (NO) plays a causal role in endotoxin-induced dysfunction of biliary transport. Rats were treated with intraperitoneal injection endotoxin (OlllB4, 4 mg/kg). At 2 hours, the liver was excised and perfused ex vivo taurocholate (TC)-containing Krebs-Ringer solution under monitoring bile output NO perfusate tissue cyclic guanosine monophosphate (cGMP) levels as indices production. The treatment evoked marked decrease acid-dependent formation concurrent increasing output, cGMP elevation, reduction hepatic adenosine triphosphate (ATP) contents oxygen consumption. Perfusion 1 mmol/L aminoguanidine (AG), an inhibitor inducible synthase, but not L-nitroarginine methyl ester, constitutive form enzyme, significantly reversed increment concert recovery consumption ATP levels. Laser confocal microfluorography lobules using rhodamine 123 (Rh), fluoroprobe sensitive mitochondrial membrane potential, revealed that elicited significant panlobularly. AG administration potential. Collectively, up-regulation by synthase accounts for mechanism through which impairs formation, its suppression serves therapeutic strategy improvement hepatobiliary function.