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Enhancement of superoxide dismutase activity in rat lungs after hypoxic preconditioning.

Ischemic preconditioning has been proved to reduce tissue damages and benefit subsequent organ transplantation. Chronic hypoxic preconditioning was found to increase the levels of lung antioxidants. This study was to test the hypothesis that levels of lung antioxidants might increase after hypoxia which may counteract the insults of free radicals. Female Wistar rats were kept in an altitude chamber (380 torr) 15 h a day for 4 weeks (hypoxia-adapted). Controls were kept at room air pressure (sea-level). After hypoxic preconditioning, no significant difference in the levels of the oxidative markers, malondialdehyde, thiobarbituric acid reactive substances and isoprostane was seen in the lungs of the hypoxia-adapted rats compared to the sea-level controls. Both the activity and protein level of manganese superoxide dismutase were higher in hypoxia-adapted lungs. Lung manganese superoxide dismutase mRNA levels, determined by real-time RT-PCR, were not significantly different in the two groups of rats. When isolated saline-perfused lungs were prepared and treated with xanthine (500 microM) and xanthine oxidase (5 mU/ml), and the levels of free radicals in the perfusate determined by chemiluminescence, less chemiluminescence was seen in the hypoxia-adapted lung perfusate. When the vascular response was determined in this same preparation before or 45 min after xanthine/xanthine oxidase treatment, the filtration coefficient was increased in the sea-level lungs but not in the hypoxia-adapted lungs. We conclude that an increase in superoxide dismutase activity and protein levels is one of the benefits of hypoxic preconditioning.