THE BENEFICIAL EFFECT OF CYCLOSPORINE ON LIVER ISCHEMIA IN RATS

Abstract

The effect of pretreatment with cyclosporine on normothermic liver ischemia was studied in rats. The rats were divided into two groups. In groups I, the animals were subjected to 60 min of warm liver ischemia. In group II, CsA (10 mg/kg, p.o.) was given daily for 4 days before induction of liver ischemia. The survival rates, serum biochemical parameters, and extent of necrosis (% liver necrosis), mitotic activities, and histology of the livers were investigated from days 1 to 7 following the release of hepatic vascular occlusion. CsA pretreatment significantly improved the survival of the animals (75.8%) in comparison with the control (42.5%). The highest levels of serum transaminases in group II had a tendency to be lower than in group I. The extent of liver necrosis reached a maximum in both groups one day postsurgery when the transaminases rose highest; however, the peak value of percentage of liver necrosis was significantly ameliorated by CsA treatment (27.1%) as compared with the control (48.3%). Furthermore, mitosis of hepatocytes in the group treated with CsA was substantially increased at day 3. Histological alterations of the livers coincided with the changes in other parameters.Our results demonstrate that CsA is capable of protecting the liver from ischemic insult. The mechanisms by which CsA exerts its beneficial effect on normothermic liver ischemia are discussed.