Implication of superoxide radicals on ischemia-reperfusion-induced skeletal muscle injury in rats.
This study was designed to clarify the mechanism of ischemia-reperfusion injury to skeletal muscle using long-acting polyoxyethylene-modified superoxide dismutase (SOD-POE) in rats. The gastrocnemius muscles of male Lews rats were investigated. Tissue levels of ATP decreased to 20% of nonischemic values after 3 h ischemia and returned to 94% after 1 h reperfusion. In contrast, they decreased to 3.5% after 4 h ischemia and remained at 20% after 1 h reperfusion. Although SOD-POE did not affect the decrease of ATP during ischemia, it improved significantly the recovery of ATP: 28%. Tissue levels of lipid peroxides (LPO) after 3 h ischemia and 1 h reperfusion did not change significantly compared with the nonischemic levels (0.71 +/- 0.32 nmol/mg protein, mean +/- SD). They showed no increase after 4 h ischemia, but increased explosively after 1 h reperfusion (2.15 +/- 0.73 nmol/mg protein). SOD-POE did not affect LPO levels during ischemia but prevented the increase of LPO significantly after reperfusion (0.98 +/- 0.25 nmol/mg protein). Xanthine oxidase activity did not increase after 3 h ischemia (22.3 +/- 7.0 mU/g) compared with the nonischemic values (17.6 +/- 10.0 mU/g). In contrast, it increased 2.5-fold after 4 h ischemia (50.1 +/- 13.7 mU/g) and remained at a significantly high level after 1 h reperfusion. SOD-POE did not affect xanthine oxidase activity during ischemia and reperfusion. These results suggest that lipid peroxidation by superoxide radicals produced by xanthine oxidase is a contributory factor to ischemia-reperfusion injury to skeletal muscle, and the clinical application of SOD-POE might be expected.
Department of Orthopedic Surgery, Faculty of Medicine, University of Nagoya, Japan.
S
S
Kawasaki
S
S
Sugiyama
N
N
Ishiguro
T
T
Ozawa
T
T
Miura
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D016166:Free Radical Scavengers; D005609:Free Radicals; D007511:Ischemia / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000098:blood supply / Q000293:injuries* / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism
D000227:Adenine Nucleotides; D016166:Free Radical Scavengers; D005609:Free Radicals; D008054:Lipid Peroxides; D010725:Phosphocreatine; D013481:Superoxides; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; D014969:Xanthine Oxidase