Biotechnology Research Institute, Universiti Malaysia Sabah, Kota-Kinabalu, Sabah, Malaysia.
Food Chem Toxicol. 2010 Dec;48(12):3345-53. doi: 10.1016/j.fct.2010.09.003. Epub 2010 Sep 7.
Diazinon (O,O-diethyl-O-[2-isopropyl-6-methyl-4-pyrimidinyl] phosphoro thioate), an organo-phosphate insecticide, has been used worldwide in agriculture and domestic for several years, which has led to a variety of negative effects in non target species including humans. However, its nephrotoxic effects and mechanism of action has not been fully elucidated so far. Therefore, the present study was aimed at evaluating the nephrotoxic effects of diazinon and its mechanism of action with special reference to its possible ROS generating potential in rats. Treatment of rats with diazinon significantly enhances renal lipid peroxidation which is accompanied by a decrease in the activities of renal antioxidant enzymes (e.g. catalase, glutathione peroxidise, glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione S-transferase) and depletion in the level of glutathione reduced. In contrast, the activities of renal γ-glutamyl transpeptidase and quinone reductase were increased. Parallel to these changes, diazinon treatment enhances renal damage as evidenced by sharp increase in blood urea nitrogen and serum creatinine. Additionally, the impairment of renal function corresponds histopathologically. In summary, our results indicate that diazinon treatment eventuates in decreased renal glutathione reduced, a fall in the activities of antioxidant enzymes including the enzymes involved in glutathione metabolism and excessive production of oxidants with concomitant renal damage, all of which are involved in the cascade of events leading to diazinon-mediated renal oxidative stress and toxicity. We concluded that in diazinon exposure, depletion of antioxidant enzymes is accompanied by induction of oxidative stress that might be beneficial in monitoring diazinon toxicity.
敌敌畏（O,O-二乙基-O-[2-异丙基-6-甲基-4-嘧啶基]硫逐磷酸酯）是一种有机磷杀虫剂，多年来在农业和家庭中在世界范围内使用，这导致了包括人类在内的多种非目标物种的各种负面影响。然而，迄今为止，其肾毒性作用及其作用机制尚未完全阐明。因此，本研究旨在评估敌敌畏的肾毒性作用及其作用机制，特别是其在大鼠体内产生 ROS 的可能性。用敌敌畏处理大鼠可显著增强肾脏脂质过氧化作用，同时伴有肾脏抗氧化酶（如过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、葡萄糖-6-磷酸脱氢酶、谷胱甘肽 S-转移酶）活性降低和还原型谷胱甘肽水平耗竭。相比之下，肾脏γ-谷氨酰转肽酶和醌还原酶的活性增加。与这些变化平行的是，敌敌畏处理增强了肾脏损伤，表现为血尿素氮和血清肌酐急剧升高。此外，肾功能的损害与组织病理学相符。总之，我们的结果表明，敌敌畏处理会导致肾脏还原型谷胱甘肽减少，抗氧化酶活性下降，包括参与谷胱甘肽代谢的酶，以及氧化物质的过度产生，同时伴有肾损伤，所有这些都参与了导致敌敌畏介导的肾脏氧化应激和毒性的级联反应。我们得出结论，在敌敌畏暴露中，抗氧化酶的耗竭伴随着氧化应激的诱导，这可能有助于监测敌敌畏毒性。
