Burk R F, Lawrence R A, Lane J M
J Clin Invest. 1980 May;65(5):1024-31. doi: 10.1172/JCI109754.
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.
百草枯和敌草快可促进生物系统中超氧阴离子的形成，脂质过氧化被认为是它们的毒性机制。已表明百草枯对缺硒小鼠的毒性比对对照小鼠更大，这可能是由于硒酶谷胱甘肽过氧化物酶活性降低所致。本研究旨在测定脂质过氧化，并评估给予百草枯和敌草快的对照大鼠和缺硒大鼠的毒性。通过测定完整动物的乙烷产生率来测量脂质过氧化；通过存活率以及肝脏和肾脏坏死的组织学和血清酶证据来评估毒性。百草枯和敌草快对缺硒大鼠的毒性均比对对照大鼠大得多。敌草快（19.5 μmol/kg）在缺硒大鼠中引起迅速且大量的肝脏和肾脏坏死以及非常高的乙烷产生率。百草枯（78 μmol/kg）的作用与敌草快相似，但不那么严重。对照大鼠中急性致死剂量的百草枯（390 μmol/kg）和敌草快（230 μmol/kg）导致极少的乙烷产生且无肝脏坏死迹象。这些发现表明，百草枯和敌草快在缺硒大鼠中的急性毒性主要通过脂质过氧化发挥作用。缺硒对红细胞或肝脏或肾脏的105,000 g上清液中的超氧化物歧化酶活性没有影响。谷胱甘肽过氧化物酶是动物体内硒唯一具有充分特征的生化功能，通过一项时间进程研究将其与硒对敌草快诱导的脂质过氧化和毒性的保护作用分离开来，在该研究中，给缺硒大鼠注射50 μg硒，随后给予敌草快（19.5 μmol/kg）。在10小时内，硒注射提供了显著的保护作用，防止敌草快诱导的脂质过氧化和死亡，尽管这种处理在10小时时并未导致肝脏、肾脏和肺或血浆中的谷胱甘肽过氧化物酶活性升高。这表明除了谷胱甘肽过氧化物酶之外，还存在一种依赖硒的因子可保护免受脂质过氧化。
