Effect of simvastatin in hepatic ischemia and reperfusion in rats

Abstract

Purpose: Liver injury induced by ischemia and reperfusion is frequently observed in the immediate postoperative period in liver transplantation and partial hepatectomy, when the liver is subjected to a period of partial or total ischemia at various times. The present study aimed to evaluate the effect of simvastatin in preventing liver ischemia-reperfusion injury in rats, using the biodistribution of radiopharmaceuticals, biochemical, immunological and histological analysis. Methods: Eighteen Wistar rats were randomly divided into three equal groups of six each. Group sham; Group IR (isquemia of left and medium hepatic lobes for 45 min; reperfusion for 24 hs); and IR simvastatin group. Animals from IR simvastatin group were treated with simvastatin microemulsion at a dose of 10mg/kg v.o. (gavage) once daily for 5 days before ischemia and reperfusion (IR). Results: Both the right and the left hepatic lobe had higher uptake of fitate-99mTc04 radioactivity in group IR simvastatin than in group IR (p<0.05). The plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactic dehydrogenase (LDH) were measured at the end of each experiment. Simvastatin pretreatment led to a profound decrease in plasma enzyme levels compared with IR rats (p≤0.001). Histopathological examination revealed necrotic areas predominantly in the perivenular zone, cytoplasm vacuolization and sinusoidal congestion in an IR group rats. Simvastatin pretreatment strongly protected livers from these changes. Conclusion: In summary, our study provides the evidence that pretreatment with simvastatin protected rat livers from ischemia/reperfusion injury in vivo. This protective effect was validated by a decrease of plasma liver enzymes and histopathological features of liver injury, as well as by biodistribution of fitate-Tc99m in liver tissue.