A novel inhibitor of inducible nitric oxide synthase (ono-1714) prevents critical warm ischemia-reperfusion injury in the pig liver

Abstract

These results indicated that ONO-1714 improved the survival rates and attenuated I/R injury in a critical hepatic warm I/R model of the pig. ONO-1714 will be beneficial for hepatectomy or liver transplantation in the clinical field.

Molecular Mediators of Liver Ischemia and Reperfusion Injury: A Brief Review

“…Indeed, use of iNOS inhibitors, such as FK330 (FR260330), reduced leukocyte activation, hepatic apoptosis, and overall liver IRI in a rat liver transplant model (58). Another iNOS inhibitor, ONO-1714, similarly attenuated liver IRI (59). Collectively, data suggest a balance between the quantity, duration, and timing of NO expression in liver IRI.…”

Nitric Oxide Synthase in Heart and Thoracic Aorta After Liver Ischemia and Reperfusion Injury: An Experimental Study in Rats

“…[9][10][11] Even though NO is an important mediator of local reperfusion injury and local NOS expression is clearly modified by liver IR, the effects of liver IR in NOS expression in remote organs are poorly recognized. [12][13][14][15] We studied the effects of liver IR damage in the immunohistochemical expression of NOS in rat thoracic aortas and hearts. Rats experienced severe liver IR injury, which was confirmed by measuring the release of ALT and AST, and the elevated hepatic tissue lipid peroxide in ischemic and nonischemic liver.…”

L-arginine in the ischemic phase protects against liver ischemia-reperfusion injury

“…In animal models of IRI, inhibitors of NOS promote tissue injury 11 . However, high tissue levels of NO may also have harmful effects [12][13][14][15][16] . Collectively, these observations suggest a balance between the local NO concentration and the time of NO exposure in determining the outcome of liver IRI 8 .…”

“…Collectively, these observations suggest a balance between the local NO concentration and the time of NO exposure in determining the outcome of liver IRI 8 . Irrespective of the precise mechanisms involved, increased inflammation and cytotoxicity are key components in hepatocellular dysfunction during the pathogenesis of liver IRI [16][17][18][19][20] .…”

“…The LG-NOS pathway has been critically implicated in liver IRI, and most studies have suggested that intravenous LG infusion increases NO levels and protects the liver against damage due to IRI [8][9][10][11][12][13][14][15][16][17][18][19][20] .…”