An increased production of reactive oxygen species has been postulated as a major pathogenic factor in the tissue damage occurring in high oxygen environment. Azide could enhance the oxygen toxicity by inhibiting superoxide dismutase and
catalase,
enzymes which remove reactive oxyge species. Mice were treated with azide (8.1 mg/kg body weight), and placed in a chamber saturated with 100%. O2 for 3, 6, 12, 24, 48 or 72 h. Superoxide radical generation, and activities of xanthine oxidase,
superoxide dismutase and catalase in homogenate of the mouse kidney were measured. Superoxide radical generation was enhanced after exposing mice to azide/100% O2, and reached to a maximum and 24 h. The elevated activity of cytosolic Cu,
Zn-superoxide
dismutase by the azid/oxyygen treatment was sustained up to 12 h. Mitochondrial Mn-superoxide dismutase was slowly induced by the azide/oxygen treatment and was continuously increased until 72 h of exposing 100% O2, while treatment with neigher
azide
nor oxygen alone enhanced the enzyme activity. Change of the catalase activity was not observed in the mouse kidney treated with azide and/or 100% oxygen. Xanthine oxidase activity was markedly decreased by the azide/oxygen treatment. These
results
suggested that superoxide radicals generated in high oxygen tensio were oxygen tension were originated mainly from mitochondria, not from xanthine oxidase-catalyzed reaction. Thus, mitochondrial Mn-superoxide dimutase was induced to remove the
superoxide radicals effectively.
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