Neurohepatic toxicity of subacute manganese chloride exposure and potential chemoprotective effects of lycopene
Neurohepatic toxicity of subacute manganese chloride exposure and potential chemoprotective effects of lycopene
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DOI：
10.1016/j.neuro.2011.12.008
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发表时间：
2012-01-01
期刊：
影响因子：
3.4
通讯作者：
El-Sayed, Yasser S.
中科院分区：
文献类型：
--
作者：
Lebda, Mohamed A.;El-Neweshy, Mahmoud S.;El-Sayed, Yasser S.
过量的锰（Mn）具有潜在的毒性，导致永久性神经退行性疾病，临床上称为“锰中毒”，其特征在于肝性脑病。本研究旨在探讨亚急性锰暴露对脑和肝组织的毒性影响，以及番茄红素在避免这种神经肝损伤方面的相对能力。大鼠每天腹腔注射MnCl 2（0或6 mg/kg，i. p.）番茄红素给药（0或10 mg/kg，p.o.）后20天，染毒4周后处死。MnCl 2诱导的脂质过氧化和抗氧化系统的扰动，增加乙酰胆碱酯酶，氨基转移酶，碱性磷酸酶和乳酸脱氢酶的活性降低与高血糖症所证明的阿尔茨海默氏II型星形胶质细胞增多症，门静脉周围肝坏死和细胞凋亡被番茄红素阻止。然而，番茄红素并没有防止身体负担的Mn和改变Fe和Cu的稳态诱导氯化锰。谷胱甘肽S-转移酶和过氧化氢酶的活动，谷胱甘肽含量减少氯化锰挑战的大鼠，并持续番茄红素。我们的研究结果表明，虽然番茄红素未能降低锰浓度或保留干扰元素的状态，它似乎是一个非常有效的，通过防止脂质过氧化反应，高血糖症和乙酰胆碱酯酶和肝胆酶的活性变化，抗氧化途径，在减轻其神经肝的有害影响。(C)2011 Elsevier Inc. All rights reserved.
Excess manganese (Mn) is potentially toxic resulting in a permanent neurodegenerative disorder, clinically known as "manganism" that is distinctive for hepaticencephalopathy. The present study was designed to explore the toxic impacts of subacute Mn exposure on brain and liver tissues, and the relative abilities of lycopene in averting such neurohepatic damage. Rats were daily injected with MnCl2 (0 or 6 mg/kg, i.p.) 20 days after lycopene administration (0 or 10 mg/kg, p.o.), and killed 4 weeks after MnCl2 exposure. MnCl2-induced lipid peroxidation and perturbation in antioxidant system, increase of acetylcholinesterase, aminotransferases, and decrease alkaline phosphatase, and lactate dehydrogenase activities with hyperglycemia as demonstrated by Alzheimer type II astrocytosis, and periportal hepatic necrosis and apoptosis were prevented by lycopene. However, lycopene did not prevent the increased body burden of Mn and the altered Fe and Cu homeostasis induced by MnCl2. Glutathione S-transferase and catalase activities, and glutathione content were reduced in MnCl2-challenged rats, and sustained by lycopene. Our results indicate that although lycopene failed to reduce Mn concentration or retain disturbed elemental status; it appears to be a highly effective in alleviating its neurohepatic deleterious effects by preventing lipid peroxidation, hyperglycemia and changes in the activity of acetylcholinesterase and hepatobiliary enzymes, and antioxidant pathways. (C) 2011 Elsevier Inc. All rights reserved.