Awad J A, Burk R F, Roberts L J
Department of Medicine, Vanderbilt University, Nashville, Tennessee.
J Pharmacol Exp Ther. 1994 Sep;270(3):858-64.
The dipyridyl herbicide diquat undergoes redox cycling in vivo resulting in superoxide generation. Diquat administration causes hepatic and renal toxicity in rodents. Selenium deficiency worsens this injury and lipid peroxidation is a prominent feature of the toxicity. However, there is limited data regarding the role of lipid peroxidation in diquat-induced toxicity in selenium-adequate animals. In addition, little is known about the effect of glutathione-modulating agents on diquat-induced toxicity and lipid peroxidation in vivo. F2-isoprostanes are novel prostanoids which, both free in plasma and esterified to phospholipids in tissues, are markers of lipid peroxidation in vivo. By using F2-isoprostane quantitation, we examined the effects of selenium deficiency and modulation of glutathione status with 1,3-bis (2-chloroethyl)-1-nitrosourea, phorone or buthionine sulfoximine on diquat-induced toxicity and lipid peroxidation. F2-isoprostanes increased 2- to 9-fold in plasma, liver, kidney and lung in selenium-adequate Fischer 344 rats with liver injury after receiving 100 mumol of diquat per kg. Selenium deficiency or modulation of glutathione status increased diquat toxicity. This was accompanied by 10- to 100-fold increases in plasma and kidney F2-isoprostane levels. Liver F2-isoprostanes were increased 2- to 5-fold. These studies suggest that glutathione, in addition to selenium, is an important defense against diquat-induced toxicity and lipid peroxidation.
联吡啶类除草剂敌草快在体内进行氧化还原循环，导致超氧化物生成。给予敌草快会使啮齿动物出现肝毒性和肾毒性。硒缺乏会加重这种损伤，脂质过氧化是毒性的一个突出特征。然而，关于脂质过氧化在硒充足动物的敌草快诱导毒性中的作用的数据有限。此外，关于谷胱甘肽调节剂对体内敌草快诱导的毒性和脂质过氧化的影响知之甚少。F2-异前列腺素是一类新型前列腺素，在血浆中游离以及在组织中与磷脂酯化，是体内脂质过氧化的标志物。通过使用F2-异前列腺素定量分析，我们研究了硒缺乏以及用1,3-双（2-氯乙基）-1-亚硝基脲、佛尔酮或丁硫氨酸亚砜胺调节谷胱甘肽状态对敌草快诱导的毒性和脂质过氧化的影响。在每千克体重接受100微摩尔敌草快后，肝脏受损的硒充足的Fischer 344大鼠的血浆、肝脏、肾脏和肺中的F2-异前列腺素增加了2至9倍。硒缺乏或谷胱甘肽状态的调节增加了敌草快的毒性。这伴随着血浆和肾脏中F2-异前列腺素水平增加10至100倍。肝脏中的F2-异前列腺素增加了2至5倍。这些研究表明，除了硒之外，谷胱甘肽也是抵御敌草快诱导毒性和脂质过氧化的重要防线。
