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Implication of superoxide radicals on ischemia-reperfusion-induced skeletal muscle injury in rats
S Kawasaki1, S Sugiyama, N Ishiguro
1Department of Orthopedic Surgery, Faculty of Medicine, University of Nagoya, Japan.
Abstract:
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.
Insights
Long-acting polyoxyethylene-modified superoxide dismutase (SOD-POE) protects skeletal muscle from ischemia-reperfusion injury by reducing lipid peroxidation. SOD-POE improved ATP recovery and prevented lipid peroxide increases post-reperfusion in rat models.
Area of Science:
- Biomedical Science
- Skeletal Muscle Physiology
- Oxidative Stress Research
Background:
- Ischemia-reperfusion injury (IRI) is a significant clinical challenge affecting skeletal muscle.
- Superoxide radicals and lipid peroxidation are implicated in IRI pathogenesis.
- Effective therapeutic strategies for mitigating IRI are needed.
Purpose of the Study:
- To elucidate the mechanism of skeletal muscle IRI.
- To evaluate the efficacy of long-acting polyoxyethylene-modified superoxide dismutase (SOD-POE) in a rat model.
- To investigate the role of lipid peroxidation and xanthine oxidase in IRI.
Main Methods:
- Male Lewis rats underwent controlled ischemia and reperfusion of the gastrocnemius muscle.
- Tissue adenosine triphosphate (ATP) and lipid peroxide (LPO) levels were measured.
- Xanthine oxidase activity was assessed.
- The effects of SOD-POE administration were evaluated.
Main Results:
- ATP levels significantly decreased during prolonged ischemia and showed limited recovery post-reperfusion.
- Lipid peroxide levels increased significantly after reperfusion, particularly following extended ischemia.
- SOD-POE administration improved ATP recovery and significantly reduced post-reperfusion LPO levels.
- Xanthine oxidase activity increased during prolonged ischemia and reperfusion, but was not affected by SOD-POE.
Conclusions:
- Lipid peroxidation, driven by superoxide radicals from xanthine oxidase, contributes to skeletal muscle IRI.
- SOD-POE demonstrates potential as a therapeutic agent to mitigate IRI by inhibiting lipid peroxidation.
- Further clinical investigation into SOD-POE for IRI treatment is warranted.