Alanine / analogs & derivatives* ; Alanine / therapeutic use ; Alanine Transaminase / blood ; Allopurinol / pharmacology ; Animals ; Bile / drug effects ; Bile / metabolism ; Enzyme Inhibitors / pharmacology ; Free Radical Scavengers / pharmacology ; Lipid Peroxidation / drug effects ; Liver Diseases / drug therapy* ; Liver Diseases / pathology ; Male ; Microsomes, Liver / drug effects ; Microsomes, Liver / enzymology ; Mixed Function Oxygenases / metabolism ; NADPH-Ferrihemoprotein Reductase / metabolism ; Organ Size / drug effects ; Quinolones / therapeutic use* ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury / drug therapy* ; Reperfusion Injury / pathology ; Vitamin E / pharmacology ; Xanthine Oxidase / antagonists & inhibitors
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.