Potentiation of acute paraquat toxicity by vitamin E deficiency
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The present study evaluated the development and course of acute paraquat toxicity in rats deficient in vitamin E, a major biologic antioxidant which interrupts free radical chain reactions and blocks lipid peroxidation. Normal and vitamin E deficient rats were given 50 mg/kg paraquat dichloride in a single intraperitoneal (IP) injection. Both percent survival and duration of survival following paraquat were significantly reduced in vitamin E deficient rats. Only 1 (2.5%) of 40 vitamin E deficient rats survived 14 days compared to 12 (30%) of 40 (p < 0.001) normal rats, and deaths occurred much earlier (p < 0.001) in vitamin E deficient rats. In addition, histologic lung damage 24 to 48 h after paraquat administration was far more extensive in vitamin E deficient rats than normal rats. Vitamin E deficient rats treated (i. e., repleted) for 7 days prior to paraquat with vitamin E 1 mg/kg/day IP had a survival rate and duration of survival nearly identical to normal rats receiving paraquat. In contrast, vitamin E deficient rats treated for 3 days prior to and 3 days after paraquat administration with superoxide dismutase (SOD) 10 mg/kg bid IP had survival rates and lung histologic changes indistinguishable from vitamin E deficient rats not receiving SOD. These results (1) demonstrate that deficiency of vitamin E potentiates acute paraquat toxicity in rats, (2) indicate that this potentiation is readily reversed by administration of vitamin E but not SOD, and (3) provide in vivo evidence that paraquat toxicity may be mediated through lipid peroxidation.
Key wordsParaquat Vitamin E deficiency Lipid peroxidation Superoxide dismutase Superoxide free radical
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