Protective effects of lithium against lead-induced toxicities in multiple systems of adult mouse
Protective effects of lithium against lead-induced toxicities in multiple systems of adult mouse
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DOI：
10.1039/c5tx00071h
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发表时间：
2015-10
影响因子：
2.1
通讯作者：
Jiutao Wang;Lingzhen Song;Kaikai Li;Runchuan Yan;Xinde Hu;Wei Zhang;Yupeng Yin;Shanting Zhao
中科院分区：
文献类型：
--
作者：
Jiutao Wang;Lingzhen Song;Kaikai Li;Runchuan Yan;Xinde Hu;Wei Zhang;Yupeng Yin;Shanting Zhao
铅（Pb）是一种有毒金属污染物，其职业和环境暴露受到全球关注。本研究旨在探讨锂（Li）对体内和体外铅损伤的保护作用。为此，3月龄小鼠接受Li（250 mg/kg体重，i. p.）2 h后腹腔注射含铅水（20 mg/kg体重）。两个星期。铅对小鼠多器官造成明显的形态学损害，如肝、肾、脾肿胀、坏死等。免疫组化结果表明，与对照组或锂对照组相比，铅暴露组小鼠海马新生细胞和未成熟神经元的数量显著减少。此外，在接触铅的小鼠中，与对照组和锂处理的小鼠相比，新产生的细胞分化为神经胶质细胞的百分比更高，分化为神经元的细胞更少，存活的新生细胞更少。在接触铅的小鼠中，认知测试受损。有趣的是，在体内和体外，预先给药的锂显着减少铅诱导的病理和神经病变。具体而言，铅暴露导致的海马神经发生的减少被阻止管理的锂。此外，我们发现，预处理与锂有效地防止认知功能障碍的小鼠暴露于铅。此外，Li预处理显著改善了海马中p-GSK-3β（Ser 9）和microRNA-34 c水平的Pb诱导的耗竭。总的来说，我们的研究结果指出，锂的能力，以减轻铅引起的损害。
Occupational and environmental exposures to lead (Pb), one of the toxic metal pollutants, is of global concern. The present study aims to investigate the protective effects of lithium (Li) against Pb-induced damage in vivo and in vitro. For this purpose, 3-month-old mice received Li (250 mg per kg body weight, i.p.) and 2 hours later water containing Pb (20 mg per kg body weight, i.p.) for 2-weeks. Treatment of mice with Pb induced remarkable morphological damage in multiple organs, such as swelling and necrosis in the liver, kidney and spleen. Immunohistochemistry demonstrated that the number of newly generated cells and immature neurons in the hippocampus was significantly decreased in mice exposed to Pb when compared with those that received saline for control or Li. Furthermore, in mice exposed to Pb a higher percentage of newly generated cells differentiated into glial cells and fewer into neurons, and less newborn cells survived compared to those in controls and Li-treated mice. In mice exposed to Pb cognitive tests were impaired. Interestingly, pre-administration of Li markedly decreased Pb-induced pathological and neurological lesions in vivo and in vitro. Specifically, the reduction of hippocampal neurogenesis resulting from Pb exposure was prevented by administration of Li. In addition, we found that pretreatment with Li effectively prevented cognitive impairment in mice exposed to Pb. Furthermore, Li pretreatment significantly improved Pb-induced depletion in p-GSK-3β (Ser9) and microRNA-34c levels in the hippocampus. Collectively our findings point to the capacity of Li to attenuate Pb-induced damage.