Role of free radicals in ischemic rat liver cell injury: prevention of damage by alpha-tocopherol administration.
The present study was undertaken to determine whether alpha-tocopherol pretreatment could modify cellular free radical metabolism during hepatic ischemia and subsequent reperfusion and prolong the viability of the liver. Although ischemia of the liver for 90 minutes did not permit survival of the animals, alpha-tocopherol administration (10 mg/kg of body weight) for 3 days increased the survival rate to 45.5%. The period of ischemia was accompanied by decreases in the hepatic adenosine triphosphate (ATP) level, endogenous alpha-tocopherol, and total glutathione (reduced and oxidized) without any significant increase in endogenous coenzyme Q (CoQ) homologs (CoQ9 and CoQ10) and lipid peroxide formation. The subsequent restoration of blood flow resulted in a low recovery of ATP and marked decreases in endogenous alpha-tocopherol, total glutathione, and CoQ homologs and, on the contrary, a marked increase in lipid peroxide levels. In alpha-tocopherol-treated animals, however, resynthesis of ATP was accelerated even after 90 minutes of ischemia, and there were no changes in the levels of total glutathione or CoQ homologs or in the level of the enhanced alpha-tocopherol during the reperfusion period. The pretreatment also completely suppressed the elevation of lipid peroxide levels. These results are compatible with the assumption that cellular damage caused by hepatic ischemia can be explained by free radical reaction processes during ischemia and especially reperfusion and suggest that administration of a free radical scavenger and antioxidant, alpha-tocopherol, is effective in ischemic liver cell injury.
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D005609:Free Radicals; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D005979:Glutathione Peroxidase / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D008054:Lipid Peroxides / Q000096:biosynthesis; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014451:Ubiquinone / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
D000227:Adenine Nucleotides; D005609:Free Radicals; D008054:Lipid Peroxides; D014451:Ubiquinone; D014810:Vitamin E; D005979:Glutathione Peroxidase; D005978:Glutathione; D019803:Glutathione Disulfide