TCV-116, an angiotensin II type 1 receptor antagonist, reduces hepatic ischemia-reperfusion injury in rats

Background. In Pringle's maneuver during liver surgery and liver transplantation, ischemia-reperfusion (I/R) is an unavoidable process, and protection against hepatic I/R injury is a major unresolved problem. Therefore, various pharmacologic approaches to prevent hepatic I/R injury are currently under trial. In this study, we investigated whether TCV-116, an angiotensin 11 type I receptor antagonist, can reduce this injury. Methods. The rats were pretreated either with TCV-116 (group 1) or with the vehicle alone (group 2). The rats in group 3 were not pretreated. Thereafter, they were subjected to partial hepatic I/R. Results. After reperfusion, the mean peak plasma concentrations of aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase, and creatine kinase were lower in group 1 than in groups 2 and 3. The magnitude of hepatic injury was reduced in group 1 compared with that in groups 2 and 3. The mean peak plasma concentrations of tumor necrosis factor-a, cytokine-induced neutrophil chemoattractants-1, and interleukin-6 were lower in group I than in groups 2 and 3. The number of neutrophils infiltrating the liver was also lower in group 1 than in groups 2 and 3. The mean peak plasma concentration of hepatocyte growth factor (HGF) was higher in group 1 than in groups 2 and 3. Conclusions. TCV-116 reduced the hepatic I/R injury by inhibiting inflammatory cytokine production and by enhancing HGF production.