Neuroprotection by luteolin and gallic acid against cobalt chloride-induced behavioural, morphological and neurochemical alterations in Wistar rats
Neuroprotection by luteolin and gallic acid against cobalt chloride-induced behavioural, morphological and neurochemical alterations in Wistar rats
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DOI：
10.1016/j.neuro.2019.07.005
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发表时间：
2019-09-01
期刊：
影响因子：
3.4
通讯作者：
Adebiyi, O. E.
中科院分区：
文献类型：
--
作者：
Akinrinde, A. S.;Adebiyi, O. E.
由职业暴露和金属植入物离子释放引起的钴（Co）中毒与神经系统改变有关，如认知能力下降、不协调和抑郁。本研究评价了木犀草素（Lut; 100 mg/kg）和没食子酸（GA; 120 mg/kg）对氯化钴（CoCl 2）连续7 d染毒Wistar大鼠的神经保护作用机制。结果表明，氯化钴诱导的神经行为缺陷，特别是减少探索活动的氯化钴暴露大鼠，焦虑增加，以及悬挂潜伏期显着减少。然而，与Lut或GA的共治疗将这些参数恢复到接近正常对照的值。此外，Lut和GA防止CoCl 2诱导的过氧化氢（H2 O2），丙二醛（MDA）和一氧化氮（NO）在脑中的增加，同时还恢复乙酰胆碱酯酶，谷胱甘肽S-转移酶（GST）和超氧化物歧化酶（SOD）的活性。此外，Lut和GA显著逆转了CoCl 2诱导的血清白细胞介素1 β（IL-1 β）和肿瘤坏死因子（TNF α）水平升高。同时，免疫组化显示星形胶质细胞表达胶质细胞酸性蛋白（GFAP），强烈的钙结合蛋白（CB）D-28 k染色和浦肯野细胞明显的树突。与此相反，CoCl 2组的特点是表达CB和树突损失的神经元数量减少。两者合计，机制毛地黄黄酮和/或没食子酸保护钴毒性涉及恢复Ca 2+稳态，乙酰胆碱酯酶和抗氧化酶的活性，以及抑制脑中的脂质过氧化。
Cobalt (Co) intoxication arising from occupational exposures and ion release from metal implants has been associated with neurological alterations such as cognitive decline, incoordination and depression. The present study evaluated the mechanisms of neuro-protection exerted by Luteolin (Lut; 100 mg/kg) and Gallic acid (GA; 120 mg/kg) in Wistar rats exposed to cobalt chloride (CoCl2) at 150 mg/kg for 7 consecutive days. Results indicate that CoCl2 induced neuro-behavioural deficits specifically by decreasing exploratory activities of CoCl2-exposed rats, increased anxiety, as well as significant reduction in hanging latency. Co-treatment with Lut or GA, however, restored these parameters to values near those of normal controls. Moreover, Lut and GA prevented CoCl2-induced increases in hydrogen peroxide (H2O2), malondialdehyde (MDA) and nitric oxide (NO) in the brain, while also restoring the activities of acetylcholinesterase, glutathione S-transferase (GST) and superoxide dismutase (SOD). In addition, Lut and GA produced significant reversal of CoCl2.induced elevation in levels of serum Interleukin 1 beta (IL-1 beta) and Tumor necrosis factor (TNF alpha). Meanwhile, immunohistochemistry revealed increased astrocytic expression of glial fibrillary acidic protein (GFAP), with intense calbindin (CB) D-28k staining and pronounced dendrites in the Purkinje cells. In contrast, the CoCl2 group was characterized by decreased number of neurons expressing CB and dendritic loss. Taken together, mechanisms of luteolin and/or gallic acid protection against Co toxicity involved restoration of Ca2+ homeostasis, acetylcholinesterase and antioxidant enzyme activities, as well as inhibition of lipid peroxidation in the brain.