Arbutin attenuates monosodium L-glutamate induced neurotoxicity and cognitive dysfunction in rats
Arbutin attenuates monosodium L-glutamate induced neurotoxicity and cognitive dysfunction in rats
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DOI：
10.1016/j.neuint.2021.105217
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发表时间：
2021-10-26
影响因子：
4.2
通讯作者：
Kushwah, Ajay Singh
中科院分区：
文献类型：
--
作者：
Kumar, Manish;Kumar, Anil;Kushwah, Ajay Singh
兴奋性毒性、氧化应激和神经炎症是神经退行性脑疾病的发病机制。虽然l -谷氨酸是参与多种脑功能的主要兴奋性神经递质，但突触过量可激活细胞死亡机制。先前的研究表明熊果苷对代谢、心血管和胃肠道疾病有缓解作用。最近，熊果苷在癫痫、帕金森病和阿尔茨海默病的动物模型中显示出益处，进一步扩大了其治疗脑部疾病的潜力。在本研究中，我们旨在评估熊果苷对大鼠味精神经毒性的潜在作用。雄性Wistar大鼠，180 ~ 200 g，分别腹腔注射味精（4 mg/kg）和熊果苷（50和100 mg/kg） 21 d。认知功能评估采用高架+迷宫和新目标识别任务。采用全脑法测定氧化应激生化指标、肿瘤坏死因子- α (tnf - α)、γ -氨基丁酸（GABA）、乙酰胆碱酯酶（AChE）活性、乳酸脱氢酶（LDH）及细胞内阳离子水平（Na+、Ca2+、K+）。味精增加了大脑中的阳离子水平、氧化应激、炎症、乙酰胆碱酯酶和乳酸脱氢酶活性，并降低了GABA水平。熊果苷（50和100 mg/kg， i.p）显著降低了味精给药大鼠大脑中的这些生化紊乱。行为学结果显示，味精引发的认知缺陷被熊果苷显著减轻。海马和皮层的组织病理学结果显示熊果苷治疗对味精的神经保护作用。MK-801和N(G)-硝基-L-精氨酸甲酯（L NAME）增强熊果苷和味精处理大鼠的记忆和神经保护作用。熊果苷可能通过抑制兴奋毒性途径在神经退行性脑疾病中提供治疗优势。
Excitotoxicity, oxidative stress, and neuro-inflammation underlie the pathogenesis of neurodegenerative brain disorders. Although L-glutamate is the prime excitatory neurotransmitter involved in diverse brain functions, however, overabundance at synapse can activate cell death mechanisms. Previous studies indicate that arbutin affords relief in metabolic, cardiovascular, and gastrointestinal disorders. Recently, arbutin showed benefits in animal models of epilepsy, Parkinson's disease, and Alzheimer's disease that further expanded its therapeutic potential against brain disorders. In the present study, we aimed to evaluate the potential of arbutin against monosodium L-glutamate (MSG) neurotoxicity in rats. Wistar rats (male, 180-200 g) were administered MSG (4 mg/kg) and arbutin (50 and 100 mg/kg) intraperitoneally for 21 days. Cognitive functions were assessed using elevated plus maze and novel object recognition task. Biochemical parameters of oxidative stress, tumour necrosis factor-alpha (TNF-alpha), gamma-amino butyric acid (GABA), acetylcholinesterase (AChE) activity, lactate dehydrogenase (LDH), and intracellular cation-levels (Na+, Ca2+, K+) were determined using whole brain. Administration of MSG augmented cation-levels, oxidative stress, inflammation, AChE, and LDH activities, and decreased GABA levels in the brain. Arbutin (50 and 100 mg/kg, i.p.) significantly decreased these biochemical disturbances in the brain of MSG administered rats. Behavioural results showed that MSG triggered cognitive deficits in rats that were significantly attenuated by arbutin. Histopathological findings in hippocampus and cortex revealed neuroprotective outcome of arbutin treatments against MSG. MK-801 and N(G)-nitro-L-arginine methyl ester (L NAME) enhanced memory and neuroprotective effects in rats treated with arbutin and MSG. Arbutin may afford therapeutic advantages in neurodegenerative brain disorders by suppressing the excitotoxic pathways.