Department of Basic Medical Sciences, Achievers University, Owo, Ondo State, Nigeria.
Department of Pharmacology and Therapeutics, Faculty of Basic Medical Science, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria.
Pestic Biochem Physiol. 2021 Jun;175:104833. doi: 10.1016/j.pestbp.2021.104833. Epub 2021 Mar 26.
Neurochemical and ATPase deregulations play important role in toxicant-induced neurodegeneration. Previous studies have shown that loss of ATPase ionic-pumps alters neurochemical balance via increased ammonia, oxidative and nitrosative stress. Thus, this study investigated the ameliorative potentials of quercetin on neurochemical, ATPase changes, hyperammonemia and oxidative/nitrosative status in the brains of Wistar rats exposed to endosulfan, a known toxic environmental pesticide that is casually used in many developing countries. Adult rats were divided into five treatment groups (n = 5). Groups 1-2 received normal saline and corn oil (vehicle) (10 mL/kg/day), group 3 received quercetin (20 mg/kg/day) orally for 28 days consecutively. However, animals in groups 4-5 were given endosulfan (5 mg/kg/day, p.o) for 28 days. But, from the 14th to 28th day, group 4 additionally received vehicle (10 mL/kg/day, p.o.), while group 5 was treated with quercetin (20 mg/kg/day, p.o.). Thereafter, brain levels of neurochemicals, ATPase activities, ammonia and oxidative/nitrosative stress were investigated by employing standardized biochemical assay protocols. Quercetin increased endosulfan-induced decreased levels of norepinephrine, dopamine, GABA, and decreased elevated concentrations of glutamate and serotonin. Quercetin normalized the increased levels of acetylcholinesterase and ammonia. Furthermore, quercetin significantly reversed the decrease in Na/K, Ca, Mg-ATPase activities induced by endosulfan. Also, quercetin increased superoxide dismutase, catalase and glutathione peroxidase activities, and reduced nitrite and peroxynitrite levels in brains of rats. These findings further provide evidence of the ameliorative potential of quercetin against endosulfan-induced neurotoxicity via attenuation of neurochemical, ATPase changes, and inhibition of acetylcholinesterase activity, ammonia release and oxidative/nitrosative stress in rat brains.
神经化学和 ATP 酶的失调在毒物诱导的神经退行性变中起着重要作用。先前的研究表明，ATP 酶离子泵的丧失通过增加氨、氧化和硝化应激来改变神经化学平衡。因此，本研究探讨了槲皮素对暴露于硫丹的 Wistar 大鼠大脑神经化学、ATP 酶变化、高氨血症和氧化/硝化状态的改善潜力，硫丹是一种已知的有毒环境农药，在许多发展中国家被随意使用。成年大鼠被分为五组（每组 5 只）。第 1-2 组每天给予生理盐水和玉米油（载体）（10ml/kg），第 3 组连续 28 天每天口服给予槲皮素（20mg/kg）。然而，第 4-5 组动物每天给予硫丹（5mg/kg，po）28 天。但是，从第 14 天到第 28 天，第 4 组动物另外给予载体（10ml/kg，po），而第 5 组动物给予槲皮素（20mg/kg，po）。然后，采用标准化生化分析方法检测各组大鼠大脑神经化学物质、ATP 酶活性、氨和氧化/硝化应激水平。槲皮素增加了硫丹诱导的去甲肾上腺素、多巴胺、GABA 水平降低，降低了谷氨酸和血清素的升高浓度。槲皮素使乙酰胆碱酯酶和氨的升高水平正常化。此外，槲皮素显著逆转了硫丹引起的 Na/K、Ca、Mg-ATP 酶活性降低。此外，槲皮素增加了超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性，降低了大鼠大脑中的亚硝酸盐和过氧亚硝酸盐水平。这些发现进一步提供了证据，表明槲皮素通过减轻神经化学、ATP 酶变化以及抑制乙酰胆碱酯酶活性、氨释放和氧化/硝化应激，对硫丹诱导的神经毒性具有改善作用。
