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Liver injury caused by ischemia-reperfusion in the rat is attenuated by pre-treatment with simvastatin Simvastatin is a member of the therapeutic family of statins. Recent experimental studies demonstrate that treatment of animals with statins reduces the injury caused by ischemia-reperfusion of the heart, brain and kidney. There is evidence that statins interfere with several signalling pathways involved in inflammation such as: NF-kappaB, peroxisome proliferator-activated receptors, and heme-oxygenase. Here we investigate the effects of simvastatin, on the liver injury caused by ischemia-reperfusion (I/R) injury, in the rat. Male Wistar rats were randomly allocated into 4 groups as described: (1) Sham Group; (2) I/R Group: rats which were subjected to liver ischemia for 45 minutes interrupting blood supply to ¾ of the liver, followed by reperfusion for 2 h; (3) Simvastatin + I/R Group: rats which received simvastatin (1 mg/kg i.v.) 30 minutes prior to liver I/R; and (4) Simvastatin Control Groups. Blood samples were obtained at the end of reperfusion for determination of biochemical markers of liver injury and tissue samples were also collected for histology. Our results show that simvastatin reduced the increase on the level of biochemical markers for liver injury when compared to I/R group: AST (965±52 vs. 740±27 IU/l) and ALT (1000±63 IU/l vs. 535±35 IU/l). We demonstrate here that simvastatin, an inhibitor of HMG-CoA reductase and a ligand of PPAR-alfa and PPAR-gama, causes a substantial reduction in the ischemia-reperfusion-induced increase in the serum levels of hepatic injury markers, providing, to our knowledge for the first time, the evidence that statin administration reduces the liver injury induced by ischemia-reperfusion, in the rat. We propose that statins, such as simvastatin, may be useful in the therapy of liver injury associated with ischemia-reperfusion of the organ. |
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