EVIDENCE THAT BOTH CYCLOSPORINE AND AZATHIOPRINE PREVENT WARM ISCHEMIA-REPERFUSION INJURY TO THE RAT-LIVER

The present work was undertaken to study whether the immunosuppressive agents cyclosporin (CyA) and azathioprine (AZA) ameliorate hepatic in jury after warm ischemia. A temporary, normothermic liver ischemia was induced in female Sprague-Dawley rats. The rats were treated with CyA (10 mg/kg per day p. o.), AZA (8 mg/kg per day p. o.), or vehicles fo r 4 days before surgery. Seven-day survival rates after 60 min of isch emia improved significantly with CyA (76.2%, P < 0.005) and AZA (78.6% , P < 0.001) treatment, compared with 43.0% for the control group. The highest levels of serum aminotransferases in the treatment groups ten ded to be lower than those in the control group. The peak values for t he percentage of liver necrosis, an indicator of the extent of hepatic necrosis, in the animals treated with CyA (26.1% +/- 7.2%, mean +/- S EM) and AZA (32.1% +/- 5.7%) were significantly lower than in the cont rol group (47.4% +/- 3.7%). Lipid peroxidative damage after reperfusio n, assessed as the hepatic malondialdehyde (MDA) concentration, was si gnificantly suppressed by pretreatment with CyA and AZA. Histological findings coincided with other parameters. This study demonstrates that both AZA and CyA have beneficial effects on normothermic liver ischem ia in rats. It is suggested that the diminished lipid peroxidative dam age with these agents might be one of the mechanisms responsible for t his.