Effects of Pretreatment with Pentoxyfilline and N-acetylcysteine on Renal Injury Following Induction of Liver Ischemia-Reperfusion

Abstract

Background & Aims: Liver ischemia-reperfusion (IR) is one of the common consequences of liver surgery, especially during liver transplantation which results in organ dysfunction. Acute hepatic injury causes systematic inflammatory responses which may finally lead to functional disturbances in remote organs such as heart, lungs and kidneys. In this study, the effects of a potent inhibitor of inflammatory cytokines (pentoxyfilline, PTX) and a well known antioxidant, (N-acetylcysteine, NAC), was evaluated on renal functional damage and oxidative stress following liver IR. Method: Five groups of six male rats were used. Group one was sham operated. In group 2, 90 min liver partial ischemia was conducted by a clamp around hepatic artery and portal vein and followed by 4 hours of reperfusion. In group 3 and 4, PTX or NAC was injected intraperitoneally before the ischemia, while in group 5 both drugs were co-administered. The levels of ALT, AST, ALP, BUN and creatinine in serum as well as MDA and GSH levels in renal tissues were measured. Results: Significant increase in the serum levels of ALT, AST in IR group is indicative of liver functional damages comparing to sham operated rats. Elevated BUN levels and increased renal tissue MDA and decreased GSH levels in IR group demonstrates a significant kidney functional damage and oxidative stress comparing to sham group. Administration of PTX alone and PTX+NAC prevented the IR-induced increase in renal MDA levels. Administration of both drugs and their co-administration prevented the reduction in renal GSH levels. Conclusion: Pretreatment with PTX and NAC before liver IR induction may prevent renal oxidative stress by protection of cellular GSH concentration and a reduction in MDA levels.