Beneficial effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation

Background. Proinflammatory cytokines such as interleukin 1-beta (IL-1 beta ) and tumor necrosis factor-alpha (TNF-alpha) play an important role in the development of hepatic ischemia/reperfusion injury. FR167653 has been char acterized as a potent suppressant of IL-1 beta and TNF-alpha production. Th e aim of this study was to evaluate the effect of FR167653 on cold ischemia /reperfusion injury in rat liver transplantation. Methods. Donor livers were preserved with cold University of Wisconsin solu tion for 48 hr and transplanted orthotopically. Immediately after reperfusi on, FR167653 (1 mg/kg, FR-treated group) or normal saline solution (control group) was administered i.v.. The severity of liver injury was determined by hepatic enzyme levels as well as by histological findings. The accumulat ion of IL-1 beta and TNF-alpha mRNA in the liver was analyzed by semi-quant itative reverse transcription-polymerase chain reaction. Tissue factor expr ession was subjected to immunohistochemical analysis, Results. In the FR-treated group, release of aspartate aminotransferase and alanine aminotransferase after reperfusion was significantly lower (P < 0. 05 and P < 0,02, respectively), and histological liver injury was less prom inent, than in the control group. Accumulation of IL-1 beta and TNF-alpha m RNA was suppressed in the FR-treated liver. Tissue factor expression on Kup ffer cells and sinusoidal endothelial cells, marked in the control group, w as almost absent in the FR-treated group. Seven-day survival in the FR-trea ted group (75%) was significantly better than that in the control group (12 .5%) (P < 0.01). Conclusions. These results indicate that treatment with FR167653 ameliorate s cold ischemia/reperfusion injury in liver transplantation.