PHARMACOLOGICAL ALTERATION OF OXYGEN-INDUCED LUNG TOXICITY

The effect of eight selected drugs on oxygen-induced pulmonary injury was evaluated in the rat. Several drug treatments, including meclofenamate (5 mg/kg/day), aminophylline (15 mg/kg/day), and vitamin C (20 and 50 mg/kg/every 12 hr) were found not to alter the survival of rats in 96 to 98% oxygen. Although vitamin E deficiency has repeatedly been shown to aggravate oxygen toxicity, pharmacologic doses of vitamin E (20 and 50 mg/kg/every 12 hr) in animals maintained on a normal diet did not offer protection against oxygen-induced lung toxicity. For the remaining drug treatments, the activity of pulmonary antioxidant defense systems [superoxide dimutase (SOD), catalase (CA), glutathione peroxidase (GP), and reduced glutathione (GSH)] were analyzed to explore the possible mechanism of pharmacological alteration of oxygen toxicity. Lungs from rats treated with dexamethasone (0.4 mg/kg/day) were found to have greater oxygen-induced lung damage and significantly lower pulmonary antioxidant activity. Rats pretreated with propylthiouracil (10 mg/kg/day) showed less oxygen-induced lung damage and greater pulmonary GSH levels and CA activity. Indomethacin pretreatment did not affect the course of oxygen toxicity or the activity of pulmonary antioxidant defense systems. GSH levels were lower in lungs of rats pretreated with levothyroxine (16.7 mg/kg/day), which produced an accelerated development of pulmonary oxygen toxicity. It was concluded that modification of the activity of the pulmonary antioxidant defense systems provides a plausible mechanism in explaining pharmacological alteration of oxygen-induced pulmonary injury. © 1979.