Rebamipide ameliorates hepatic dysfunction induced by ischemia/reperfusion in rats.
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, alpha-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. Aminopyrine N-demethylase activity was decreased and aniline p-hydroxylase was increased by ischemia/reperfusion, which were prevented by alpha-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.
Lee
S M
SM
College of Pharmacy, Sung Kyun Kwan University, Suwon, South Korea.
Kim
K H
KH
D000409:Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000410:Alanine Transaminase / Q000097:blood; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008107:Liver Diseases / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D015363:Quinolones / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D014810:Vitamin E / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D015363:Quinolones; D014810:Vitamin E; D000493:Allopurinol; D006899:Mixed Function Oxygenases; D014969:Xanthine Oxidase; D009251:NADPH-Ferrihemoprotein Reductase; D000410:Alanine Transaminase; C052785:rebamipide; D000409:Alanine