Rebamipide ameliorates hepatic dysfunction induced by ischemia/reperfusion in rats

Abstract

The relationship between lipid peroxidation and alterations in hepatic secretory function and microsomal function during hepatic ischemia/reperfusion was studied. Rats pretreated with free radical scavengers were subjected to 60 min of hepatic ischemia and to 1 and 5 h of reperfusion thereafter. Serum aminotransferase level and microsomal lipid peroxidation were markedly increased by ischemia/reperfusion. These increases were significantly attenuated by rebamipide, α-tocopherol or allopurinol. Bile flow and cholate output were markedly decreased by ischemia/reperfusion and free radical scavengers, especially rebamipide, restored their secretion. NADPH-cytochrome P450 reductase activity and cytochrome P450 content were decreased by ischemia/reperfusion. Rebamipide prevented the decrease of the NADPH-cytochrome P450 reductase activity but had little effect on the cytochrome P450 content. AminopyrineN-demethylase activity was decreased and anilinep-hydroxylase was increased by ischemia/reperfusion, which were prevented by α-tocopherol and allopurinol, but not by rebamipide. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory function and microsomal function by increasing lipid peroxidation, and rebamipide significantly ameliorates these changes through its free radical scavenging activity.