Potential Hepatic Protection by Erythropoietin and Ischemic Conditioning in a Rat Model of Renal Ischemia-Reperfusion Injury

Abstract
Background: Renal ischemia reperfusion injury is a com-mon consequence of many clinical conditions including renal transplantation, sepsis, trauma, and shock and usually leads to acute kidney injury. Its adverse effects extend to other organs including the liver leading to remote organ injury. Erythropoietin and ischemic conditioning have an anti-inflammatory, anti-oxidant and anti-apoptotic effects and were reported to have a protective effect against ischemia reperfusion injury in different organs.
Aim of the Study: To evaluate the possible protective effect of erythropoietin and ischemic conditioning on the liver following renal ischemia reperfusion injury and to declare some of the possible mechanisms involved.
Material and Methods: This study was conducted on 66 adult male albino rats divided into 6 equal groups: Group I: Sham group; Group II: Renal ischemia reperfusion group (I/R); Group III: Erythropoietin pre-treatment renal ischemia reperfusion group (EPO pre-I/R); Group IV: Erythropoietin post-treatment renal ischemia reperfusion group (EPO post-I/R); Group V: Ischemic pre-conditioning-renal ischemia reperfusion group (IPC) and Group VI: Ischemic post-conditioning-renal ischemia reperfusion group (IPOC).
Results: Group II showed significant increase in serum creatinine, blood urea, blood urea nitrogen, AST and ALT levels with significant increase in renal and hepatic injury score indicating renal and hepatic injury following renal ischemia reperfusion. In the same group, a significant increase in serum IL6, TNFa, MDA and a significant decrease in serum SOD were found. Both group III and IV revealed a significant decrease in serum creatinine, blood urea, blood urea nitrogen, AST, ALT, renal and hepatic injury score. Levels of IL6, TNFa, and MDA significantly decrease and SOD significantly increased in both groups relative to group II and these changes were significantly higher in group III relative to group IV. In group V and VI, a significant decrease in serum creatinine, blood urea, blood urea nitrogen and renal injury score was found in both groups, while serum AST, ALT and hepatic injury score were significantly decreased in group VI but remained insignificantly changed in group V versus group II. Serum IL6 and TNFa significantly decreased in both groups, while MDA significantly decreased and SOD significantly increased in group VI only and no significant change was noticed in group V versus group II.
Conclusion: Erythropoietin pre and post treatment signif-icantly improved renal and hepatic function and morphology following renal ischemia reperfusion injury with better results for erythropoietin pre-treatment. Ischemic post-conditioning induced significant decrease in renal and hepatic injury, while ischemic pre-conditioning provided renal protective effect which didn't extend to involve the liver.