Penconazole (PEN) is a widely used systemic fungicide to treat various fungal diseases in plants but it leaves residues in crops and food products causing serious environmental and health problems. N-acetylcysteine (NAC) is a precursor of the antioxidant glutathione in the body and exerts prominent antioxidant and anti-inflammatory effects. The present study aimed to explore the mechanistic way of NAC to ameliorate the PEN neurotoxicity in male rats. Twenty-eight male rats were randomly divided into four groups (n = 7) and given the treated material via oral gavage for 10 days as the following: Group I (distilled water), Group II (50 mg/kg body weight [bwt] PEN), Group III (200 mg/kg bwt NAC), and Group IV (NAC + PEN). After 10 days all rats were subjected to behavioral assessment and then euthanized to collect brain tissues to perform oxidative stress, molecular studies, and pathological examination. Our results revealed that PEN exhibits neurobehavioral toxicity manifested by alteration in the forced swim test, elevated plus maze test, and Y-maze test. There were marked elevations in malondialdehyde levels with reduction in total antioxidant capacity levels, upregulation of messenger RNA levels of bax, caspase 3, and caspase 9 genes with downregulation of bcl2 genes. In addition, brain sections showed marked histopathological alteration in the cerebrum and cerebellum with strong bax and inducible nitric oxide synthetase protein expression. On the contrary, cotreatment of rats with NAC had the ability to improve all the abovementioned neurotoxic parameters. The present study can conclude that NAC has a neuroprotective effect against PEN-induced neurotoxicity via its antioxidant, anti-inflammatory, and antiapoptotic effect. We recommend using NAC as a preventive and therapeutic agent for a wide variety of neurodegenerative and neuroinflammatory disorders.

中文翻译：

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N-乙酰半胱氨酸对戊菌唑诱导的大鼠神经退行性和神经炎性疾病的改善作用

戊菌唑 (PEN) 是一种广泛使用的内吸性杀菌剂，用于治疗植物中的各种真菌病害，但它会在农作物和食品中留下残留物，造成严重的环境和健康问题。N-乙酰半胱氨酸 (NAC) 是体内抗氧化剂谷胱甘肽的前体，具有显着的抗氧化和抗炎作用。本研究旨在探索NAC改善雄性大鼠PEN神经毒性的机制途径。28只雄性大鼠随机分为四组（n = 7) 并通过口服管饲法给予处理过的材料 10 天，如下所示：I 组（蒸馏水）、II 组（50 mg/kg 体重 [bwt] PEN）、III 组（200 mg/kg bwt NAC） ，和第四组（NAC + PEN）。10天后对所有大鼠进行行为评估，然后安乐死收集脑组织进行氧化应激、分子研究和病理检查。我们的研究结果表明，PEN 表现出神经行为毒性，表现为强迫游泳测试、高架十字迷宫测试和 Y 迷宫测试的改变。丙二醛水平显着升高，总抗氧化能力水平降低，bax、caspase 3 和 caspase 9 基因的信使 RNA 水平上调，bcl2 基因下调。此外，脑切片显示大脑和小脑明显的组织病理学改变，具有强烈的bax和诱导型一氧化氮合成酶蛋白表达。相反，NAC 对大鼠的共同治疗能够改善所有上述神经毒性参数。本研究可以得出结论，NAC 通过其抗氧化、抗炎和抗凋亡作用对 PEN 诱导的神经毒性具有神经保护作用。我们建议使用 NAC 作为多种神经退行性和神经炎症性疾病的预防和治疗剂。本研究可以得出结论，NAC 通过其抗氧化、抗炎和抗凋亡作用对 PEN 诱导的神经毒性具有神经保护作用。我们建议使用 NAC 作为多种神经退行性和神经炎症性疾病的预防和治疗剂。本研究可以得出结论，NAC 通过其抗氧化、抗炎和抗凋亡作用对 PEN 诱导的神经毒性具有神经保护作用。我们建议使用 NAC 作为多种神经退行性和神经炎症性疾病的预防和治疗剂。