Paraquat and
diquat facilitate formation of
superoxide anion in
biological systems, and lipid peroxidation has been postulated to be their mechanism of toxicity.
Paraquat has been shown to be more toxic to
selenium-deficient mice than to controls, presumably as the result of decreased activity of the selenoenzyme
glutathione peroxidase. The present study was designed to measure lipid peroxidation and 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 mumol/kg) caused rapid and massive liver and kidney
necrosis and very high
ethane production rates in
selenium-deficient rats. The effect of
paraquat (78 mumol/kg) was similar to that of
diquat but was not as severe. Acutely lethal doses of
paraquat (390 mumol/kg) and
diquat (230 mumol/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 peroxidation and toxicity by a time-course study in which
selenium-deficient rats were injected with 50 mug of
selenium and later given
diquat (19.5 mumol/kg). Within 10 h, the
selenium injection provided significant protection against
diquat-induced lipid peroxidation and mortality even though this treatment resulted in no rise in
glutathione peroxidase activity of liver, kidney, lung, or plasma
at 10 h. This suggests that a
selenium-dependent factor in addition to
glutathione peroxidase exists that protects against lipid peroxidation.