Effect of Superoxide Dismutase and Dimethylthiourea on the Ultrastructure of Hepatocytes in Normothermic Hepatic Ischemia-Reperfusion Injury of Rats

ABSTRACT

BACKGROUND: Temporary interruption of blood flow to the liver is often unavoidable during operations for extensive injury of the liver or for major liver resection. Following ischemia- reperfusion, transient dysfunction of the liver occurs. It has been suggested that reactive oxygen metabolites play an important role in microvascular reperfusion injury. Superoxide dismutase (SOD) and dimethylthiourea (DMTU) are known to be antioxidants that scavenge oxygen free radicals to reduce microvascular reperfusion injury. This experiment studied the effect of SOD and DMTU on warm ischemia-reperfusion injury to the liver and compared inflow occlusion and hepatic vascular exclusion (HVE) after 20 minutes of ischemia. METHODS: One hundred fourteen healthy male Sprague-Dawley rats weighing around 250 g were used. The rats were divided into control (n=18) and experimental groups (n=96). The control groups included sham, SOD, and DMTU control groups. The experimental groups included inflow occlusion, SOD- pretreated inflow occlusion, DMTU-pretreated inflow occlusion, and inflow and outflow occlusion (HVE) groups. These 4 experimental groups had 24 rats each. The rats were sacrificed immediately, and at 24 hours, 48 hours, and 72 hours after reperfusion, and specimens were obtained from left anterior lobe of the liver. The specimens were prepared using routine methods for electron-microscope observations. RESULTS: The ultrastructures of the hepatocytes in all the experimental groups were similar to those of the normal control rats after just 20 minutes of ischemia. In the inflow occlusion group, dilatation and sacculation of the cisternae of the endoplasmic reticulum and mitochondria with many electron dense granules were observed in the hepatocytes after 24 hours of reperfusion. In the course of reperfusion, damage progressed until 72 hours after reperfusion. The HVE group showed more serious changes than the inflow occlusion group. The SOD- and the DMTU-treated groups showed clear attenuation of liver damage after 48 and 72 hours of reperfusion.CONCLUSION: The ultrastructural changes of hepatocytes after 20 minutes of ischemia became more prominent by prolonging the reperfusion time. The changes after hepatic inflow occlusion were less prominent than those after HVE. DMTU and SOD attenuated the injury to hepatocytes after warm ischemia-reperfusion.