Prevention of acute paraquat toxicity in rats by superoxide dismutase.
Paraquat is a widely used herbicide which causes lung injury in man characterized by progressive parenchymal damage that may lead to fatal respiratory failure. The precise mechanism of injury is unknown but is related to the cyclic oxidation and reduction of paraquat in cells with resultant production of free radicals of oxygen. In this study, superoxide dismutase (SOD), an enzyme that catalyzes the dismutations of superoxide free radical (O2-) to less toxic forms, plus reduced glutathione (GSH), and d-propranolol (PROP), were evaluated for their ability to protect against acute paraquat toxicity. Rats maintained at room air were given 50 mg paraquat dichloride/kg body weight in a single intraperitoneal (IP) injection 60 min prior to receiving either 0.2, 2, 10, or 20 mg/kg/d SOD, 3.6, 7.2, or 14.4 mmol/kg/d GSH, 2 or 20 mg/kg/d PROP, or an equal volume of normal saline (controls) LP. in divided doses for 3 d. SOD significantly prolonged and increased survival at doses of 2, 10, or 20 mg/kg/d (p less than 0.05). In addition, histologic lung morphology in SOD-treated rats showed only minimal intra-alveolar hemorrhage and hypercellularity 24, 48, and 168 h after paraquat challenge. Treatment with GSH, PROP or 0.2 mg/kg/d SOD was not protective. Duration of survival, percent survival, and lung morphology in these groups were not significantly different from controls. These results indicate that a) SOD protects against the development of acute paraquat toxicity in rats, b) one mechanism of paraquat poisoning is increased biologic production of O2-, and c) SOD may have a role in the therapy of paraquat poisoning in man.
D000818:Animals; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D010101:Oxygen Consumption; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D012119:Respiration / Q000187:drug effects; D013482:Superoxide Dismutase / Q000627:therapeutic use*
D013482:Superoxide Dismutase; D010269:Paraquat