Liver Injury Following Renal Ischemia Reperfusion in Rats

Abstract

Introduction All transplanted solid organs experience some degree of ischemia-reperfusion (I-R) injury. There is some evidence that I-R injury affects remote organs. We investigated the effects of renal I-R injury on hepatic function, cytochrome P-450 enzymes, and morphology in rats. Methods A rat model of 1 hour of renal ischemia followed by 1, 4, or 8 hours of reperfusion. The assays included serum alanine aminotransferase (sALT) aspartate aminotransferase (sAST), cytochrome P-450 enzymes (CYP3A, CYP2E1), hepatic glutathione S-transferase (GST), glutathione (GSH), malondialdehyde (MDA), superoxide dysmutase (SOD), and myeloperoxidase (MPO) activities. In addition, we measured serum blood urea nitrogen (BUN) and serum creatinine (SCr), and renal MDA, glutathione peroxidase levels, and SOD activities. Morphological liver changes were observed by optical and electron microscopy. Results sALT and sAST significantly increased after 1 hour of ischemia and 4 or 8 hours of reperfusion. Hepatic CYP3A and CYP2E1 activities were significantly decreased after 1 hour of ischemia and 1 or 4 hours of reperfusion. Hepatic GST, GSH, and SOD activities decreased after renal I-R, while MDA levels and MPO increased. Serum BUN and SCr levels significantly increased after reperfusion. Changes in renal MDA, GSH-px, and SOD activities were similar to those in the liver. The only difference between them was the peak time of injury: for the kidney, 8 hours, while for the liver, some changes appeared at 4 hours. Optical microscopy showed hepatic passive venous congestion and fatty degeneration as well as local necrosis. Transmission electronic microscope showed hepatic cell membrane was damaged, which seemed to explain some data results above. For example, the release of hepatic ALT and AST increased serum ALT and AST. More importantly, the release of neutrophil chemokine induced neutrophil accumulation in the liver, which could cause further damage. Conclusion Our findings indicated that hepatic function, cytochrome P-450 enzymes and morphology were affected by renal I-R injury. These effects seemed to be mediated in part by an imbalance of oxidant and antioxidant systems and recruitment of neutrophils to the liver.