Loghman-Hakim Hospital Poison Center, Faculty of Medicine, and Toxicological Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.
Toxicol Mech Methods. 2007;17(2):109-15. doi: 10.1080/15376510600860318.
ABSTRACT Diazinon, an organophosphate (OP) insecticide, is widely used in agriculture and domestically. Reactive oxygen species (ROS) caused by OPs are involved in the toxicity of various pesticides. The aim of the present study was to analyze the role of diazinon in inducing oxidative stress in adult male Wistar rats and to evaluate the possible protective effects of alpha-tocopherol (TPH) and the glutathione prodrug N-acetyl-cysteine (NAC) after 4 weeks of exposure to a sublethal dose of diazinon. TPH (10 mg/kg/day), NAC (160 mg/kg/day), diazinon (25 mg/kg/day), a combination of NAC (160 mg/kg/day) and diazinon (25 mg/kg/day), and a combination of TPH (10 mg/kg/day) and diazinon (25 mg/kg/day) were given to rats orally via gavage for 4 weeks. The thiobarbituric acid reactive substances (TBARS) marker of lipid peroxides levels, total thiol molecules, and total antioxidant capacity of plasma were all analyzed as biomarkers of oxidative stress. In addition, the acetylcholinesterase (AChE) activity was measured as a biomarker of toxicity. The results from this study well indicate diazinon-induced oxidative stress demonstrated by enhanced TBARS, decreased total thiol molecules, and total antioxidant capacity. In addition, AChE activity was inhibited as a marker of OP toxicity. Data show the protective roles of TPH and NAC in reducing the diazinon-induced oxidative stress. Interestingly, both TPH and NAC recovered diazinon-induced AChE inhibition. It is concluded that supplementation with TPH and NAC can reduce toxicity of OP in human exposure.
摘要 敌敌畏，一种有机磷（OP）杀虫剂，广泛应用于农业和家庭中。OP 引起的活性氧（ROS）参与了各种杀虫剂的毒性。本研究旨在分析敌敌畏在诱导成年雄性 Wistar 大鼠氧化应激中的作用，并评估生育酚（TPH）和谷胱甘肽前体 N-乙酰半胱氨酸（NAC）在接触敌敌畏亚致死剂量 4 周后的可能保护作用。TPH（10mg/kg/天）、NAC（160mg/kg/天）、敌敌畏（25mg/kg/天）、NAC（160mg/kg/天）和敌敌畏（25mg/kg/天）的混合物以及 TPH（10mg/kg/天）和敌敌畏（25mg/kg/天）的混合物通过灌胃给予大鼠，持续 4 周。脂质过氧化的硫代巴比妥酸反应物质（TBARS）标志物、血浆总巯基分子和总抗氧化能力均被分析为氧化应激的生物标志物。此外，乙酰胆碱酯酶（AChE）活性被测量为毒性的生物标志物。本研究结果表明，敌敌畏诱导的氧化应激表现为 TBARS 增加、总巯基分子和总抗氧化能力降低。此外，AChE 活性作为 OP 毒性的标志物受到抑制。数据表明 TPH 和 NAC 具有减少敌敌畏诱导的氧化应激的保护作用。有趣的是，TPH 和 NAC 均可恢复敌敌畏诱导的 AChE 抑制。因此，补充 TPH 和 NAC 可以减少 OP 在人类暴露中的毒性。
