Cytotoxic effect of oxygen on the skeletal muscle of mouse diaphragm

Incubation of the isolated mouse diaphragm with a high rate of oxygenation (10 ml s-1, 95% O2 + 5% CO2) causes a characteristic cellular damage with widely-separated myofibrils and swollen sarcotubular system within 10 min. This damage was ameliorated by inhibitors of the hydroxyl radical (.OH), desferrioxamine, dimethyl thiourea and 120 mM mannitol, and by incubation at 8 degrees C. It was not prevented either by inhibitors of the pathway leading to sarcolemma damage (nordihydroguaiaretic acid, alpha-tocopherol, butylated hydroxytoluene) nor by agents and treatments that inhibit the oxygen paradox of cardiac muscle (glucose, omission of extracellular calcium, incubation at 30 degrees C, superoxide dismutase and catalase). Nevertheless there are similarities between these two types of damage triggered by O2 and the possibility that in both an NAD(P)H oxidase is stimulated and cytotoxic oxygen radicals are generated is discussed.