Mammalian Toxicology Department, Central Agricultural Pesticides Laboratory, Agricultural Research Center, Dokki, Giza, 12618, Egypt.
Biotechnology Department, Faculty of Science, Islamic University of Gaza, Gaza, Palestine.
Neurotox Res. 2020 Apr;37(4):871-882. doi: 10.1007/s12640-020-00172-6. Epub 2020 Feb 8.
The association between gestational exposure to organophosphate and neurodevelopmental deficits is an area of particular interest, since the developing brain is sensitively susceptible to this neurotoxic pesticide. Instead, the neuroprotective role of quercetin has been suggested, but its exact protective mechanism against the developmental neurotoxicity of organophosphate did not previously notify. In this study, we have evaluated the anti-apoptotic role of quercetin against the developmental neurotoxicity of fenitrothion. Forty timed pregnant rats (from the 5th to the 19th day) were divided into four groups: control, quercetin (100 mg/kg/day), fenitrothion (2.31 mg/kg/day), and quercetin-fenitrothion co-treated groups where all animals received the corresponding doses by gavage. The embryotoxicity and many symptoms of the fetal growth retardation were recorded in the fenitrothion-intoxicated group. As compared with the control, fenitrothion brought significant (p < 0.05) elevation in the fetal brain dopamine, serotonin, and malondialdehyde levels as well as the activities of superoxide dismutase and catalase. However, fenitrothion decreased the glutathione concentration together with the activities of acetylcholinesterase, glutathione-S-transferase, and glutathione reductase. Moreover, fenitrothion induced some of the histopathological alterations in fetal brain and remarkably (p < 0.05) upregulated the mRNA gene expression of Bax and caspase-3 plus their protein immunoreactivity. It is worth mentioning that quercetin co-treatment alleviated (p ˂ 0.05) the fetal growth shortfalls, neurotransmission disturbances, lipid peroxidation, antioxidant disorders, and apoptosis evoked by fenitrothion with frequent repair to the control range. These results revealed that the downregulation of apoptosis-related genes and catecholamines is an acceptable indicator for the neuroprotective efficiency of quercetin especially during gestational exposure to organophosphate.
有机磷暴露与神经发育缺陷之间的关联是一个特别引人关注的领域，因为发育中的大脑对这种神经毒性农药非常敏感。相反，已有人提出槲皮素具有神经保护作用，但它对有机磷发育神经毒性的确切保护机制此前尚未得到通知。在这项研究中，我们评估了槲皮素对fenitrothion 发育神经毒性的抗凋亡作用。40 只孕鼠（第 5 至 19 天）分为四组：对照组、槲皮素（100mg/kg/天）组、fenitrothion（2.31mg/kg/天）组和槲皮素-fenitrothion 共同处理组，所有动物均通过灌胃给予相应剂量。在 fenitrothion 中毒组中记录了胚胎毒性和许多胎儿生长迟缓的症状。与对照组相比，fenitrothion 显著升高（p<0.05）了胎儿大脑中的多巴胺、血清素和丙二醛水平，以及超氧化物歧化酶和过氧化氢酶的活性。然而，fenitrothion 降低了谷胱甘肽浓度，同时降低了乙酰胆碱酯酶、谷胱甘肽 S-转移酶和谷胱甘肽还原酶的活性。此外，fenitrothion 诱导了胎儿大脑的一些组织病理学改变，并显著（p<0.05）上调了 Bax 和 caspase-3 的 mRNA 基因表达及其蛋白免疫反应性。值得一提的是，槲皮素共同处理减轻了（p<0.05）由 fenitrothion 引起的胎儿生长不足、神经递质紊乱、脂质过氧化、抗氧化紊乱和细胞凋亡，并经常恢复到对照范围。这些结果表明，下调凋亡相关基因和儿茶酚胺是槲皮素神经保护效率的一个可接受指标，尤其是在妊娠期接触有机磷的情况下。
