EFFECT OF ISCHEMIC PRECONDITIONING ON LIVER ISCHEMIA REPERFUSION INJURY IN AGED RATS

Abstract

Background: As the criteria for liver donation have been extended to include marginal donors, liver grafts are becoming particularly vulnerable to hepatic ischemia-reperfusion injury (IRI). However, no specific measures have been validated to ameliorate hepatic IRI. Objective: To investigate the effect of ischemic preconditioning on hepatic ischemia/reperfusion (IR) injury in aged rats. Materials and Methods: The present study was performed on 45 aged male Wistar rats, weighing at the start of the study between 350-550 g. Animals were randomly divided into the following equal groups: Group I (Sham-operated control group), Group II (Liver ischemia reperfusion group): Rats were subjected to 1-hour partial liver ischemia followed by 24-hour reperfusion and Group III (ischemic preconditioned group): Rats were subjected to brief period of ischemia and reperfusion, then were subjected to hepatic IR as group II. Blood samples were collected and were subjected to measurement of Liver function tests, i.e. serum ALT, AST, liver malondialdehyde and glutathione peroxidase. Also, histopathological study of rat livers was performed. Results: There were significant decrease in liver weight and liver weight to body weight percent in IR group compared to the sham-operated rats. Upon preconditioning before IR, the liver weights still decreased compared to the sham-operated rats. Liver weight to body weight ratio ameliorated or less decreased in the ratio compared to sham-operated, and significantly increased in the ratio compared to the IR rats. There were significant increases in serum levels of liver enzymes (ALT and AST), at two time points, especially 24 hours after reperfusion as well as significant increase in hepatic MDA level in IR rats. In addition, IR has induced marked liver damage as shown by histopathological examination. Ischemic preconditioning ameliorated liver ischemia reperfusion injury as indicated by marked reduction in the liver enzymes although their levels did not match the levels recorded in the sham-operated rats and hepatic MDA. Hepatic level of GPx showed a significant increase compared to both the sham-operated and IR rats and that was associated with significant improvement of the histopathological examination compared to IR rats. Conclusion: Ischemic preconditioning ameliorated the hepatic injury associated with ischemia reperfusion. However, future work is needed to explain the mechanism by which IPC ameliorate liver IRI.