An increased production of reactive oxygen species has been postulated as a major pathogenic factor of the tissue damage occurring in high oxygen environment, Azide could enhance the oxygen toxicity by inhibiting superoxide dismutase and
catalase,
enzymes which remove reactive oxygen species. Mice were treated intraperitoneally with azide(8.1mg/kg body weigh), 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 liver were measured. At 3 h of the treatment with azide/100% O2, superoxide radical generation was enhanced to more than 12 times of the control. Such increment was much higher
in the
liver of mice treated with both azide and 100% O2 alone. On the other hand, the activities of mitochondrial Mn-superoxide dismutase and catalase were decreased, while Cu, Zn-superoxide dismtase activity was elevated by the azide/oxygen treatment.
Xanthine oxidase activity was markedly increased by the azide/oxygen treatment. These results indicate that superoxide radical generation in the mouse liver by the aszide-/oxygen treatment may be due to the inhibiton of Mn-superoxide dismutase
and
catalase, and due to increased xanthine oxidase activity. Treatment with azide alone did not decrease the activities of Mn-superoxide dismutase and catalase. This reults suggested that azide did not effectively inhibit these enzymes in vivo.
|