Effect of Selenium Deficiency

to assess toxicity in control and selenium-deficient rats given paraquat and diquat. Lipid peroxidation was measured by determining ethane production rates of intact animals; toxicity was assessed by survival and by histological and serum enzyme evidence of liver and kidney necrosis. Paraquat and diquat were both much more toxic to selenium-deficient rats than to control rats. Diquat (19.5 umol/kg) caused rapid and massive liver and kidney necrosis and very high ethane production rates in selenium-deficient rats. The effect of paraquat (78 ,umol/kg) was similar to that of diquat but was not as severe. Acutely lethal doses of paraquat (390 ,umol/kg) and diquat (230 ,umol/kg) in control rats caused very little ethane production and no evidence of liver necrosis. These findings suggest that paraquat and diquat exert their acute toxicity largely through lipid peroxidation in selenium-deficient rats. Selenium deficiency had no effect on superoxide dismutase activity in erythrocytes or in 105,000 g supernate of liver or kidney. Glutathione peroxidase, which represents the only well-characterized biochemical function of selenium in animals, was dissociated from the protective effect of selenium against diquat-induced lipid peroxiThis work was published in part in abstract form in 1979. Gastroenterology. 76: 1109. As of 1 April 1980, Dr. Burk's address will be Department of Medicine, University of Texas Health Science Center, San Antonio, Tex. Received for publication 1 October 1979 and in revised form 26 November 1979. 1024 dation and toxicity by a time-course stuidy in which selenium-deficient rats were injected with 50 ,ug of selenium and later given diquat (19.5 ,umol/kg). Within 10 h, the selenium injection provided significant protection against diquat-induced lipid peroxidation and mortality even though this treatment resuilted in no rise in glutathione peroxidase activity of liver, kidney, lung, or plasma at 10 h. This suggests that a seleniumdependent factor in addition to glutathione peroxidase exists that protects against lipid peroxidation.