| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
Liver ischemia-reperfusion induced cellular damage caused by stimulated lipid peroxidation on biomembranes, especialy after reperfusion, which resulted in a marked decrease in ATP resynthesis after reperfusion due to mitochondrial dysfunction, and a decrease in the survival rate depending on ischemic periods. The administration of either coenzyme q_<10> (CoQ_<10>) or <alpha>-tocopherol (<alpha>-Toc) prior to ischemia completely suppressed the stimulated lipid peroxidation, and raised ATP resynthesis due to reversal of the mitochondrial dysfunction, which were accompained by a marked rise in the survival rate from 0% to 60% after 90-min ischemia. When endogenous levels of CoQ_<10> homologs (CoQ_9, CoQ_<10>), <alpha>-Toc and reduced glutathione (GSH) in the liver were determined during 90-min ischemia and following 60-min reperfusion period, the lwvels of <alpha>-Toc and GSH decreased during ischemia, which were not protected by CoQ_<10> pretreatment. The levels of endogenous antioxidant
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s tested decreased markedly after reperfution following to ischemia, which were completely reversed by the administration of either CoQ_<10> or <alpha>-Toc. These results obtained are compatible with the assumption that cellular damage caused by hepatic ischemia-reperfusion can be explained by free radical injury, and that antioxidants administered can protect cellular damage from lipid peroxidation by either radical scavenging and antioxidant actions.
The protective effect of CoQ_<10> on ischemic damage could be demonstrated with orthotopic transplantation of the rat liver subjected to warm ischemia for 30 min: the survival rate of recipient rats increased from 0% to 45% in CoQ_<10>-pretreated group.
Cellular damage due to endotoxemia was also explained, at least in part, by stimulated lipid peroidation. The administration of CoQ_<10> and <alpha>-Toc completely suppressed lipid peroxidation with a marked improvement of energy metabolism as well as endogenous levels of antioxidants, which, resulted in a marked rise of the survival rate. Less
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