Department of Environmental Health, School of Public Health, China Medical University, Shenyang 110001, PR China.
Environ Toxicol Pharmacol. 2008 Sep;26(2):232-6. doi: 10.1016/j.etap.2008.04.003. Epub 2008 Apr 26.
Manganese (Mn) is an essential trace element for human nutrition but also a toxicant when humans are exposed to high concentration. Occupational exposures to excess levels of Mn are known to cause manganism in humans. Mn is known to induce mitochondrial dysfunction in excessive dose, however the mechanisms underlying its action are not elucidated clearly. To determine the possible role of energy metabolism and oxidative stress in Mn-induced mitochondria injury, isolated mitochondria were exposed to different concentrations of MnCl(2) (5, 50, 500, 1000μmol/L), aconitase and mitochondrial complex I activities, MDA and GSH contents, MMP were investigated. In addition, effects of NAC (500μmol/L) were studied at 500μmol/L MnCl(2). Dose-dependent inhibition of aconitase and mitochondrial complex I activities, increase of MDA content, decrease of GSH content and MMP were observed. Further investigation indicated NAC pre-treatment significantly reversed toxic effect of MnCl(2). The results indicated that manganese could dose-dependently induce the decline of energy metabolism and cause oxidative damage of mitochondria isolated from rat brain, and this change could be prevented by pre-treating with NAC.
锰（Mn）是人体营养所必需的微量元素，但当人体暴露于高浓度时，它也具有毒性。已知职业性暴露于过量的锰会导致人体锰中毒。锰在过量剂量下已知会引起线粒体功能障碍，但其作用机制尚未阐明清楚。为了确定能量代谢和氧化应激在锰诱导的线粒体损伤中的可能作用，将分离的线粒体暴露于不同浓度的 MnCl₂（5、50、500、1000μmol/L）中，研究了顺乌头酸酶和线粒体复合物 I 活性、MDA 和 GSH 含量、MMP。此外，还研究了 500μmol/L MnCl₂时 NAC（500μmol/L）的作用。观察到顺乌头酸酶和线粒体复合物 I 活性的剂量依赖性抑制、MDA 含量增加、GSH 含量减少和 MMP 降低。进一步的研究表明，NAC 预处理可显著逆转 MnCl₂的毒性作用。结果表明，锰可剂量依赖性地诱导大鼠脑分离的线粒体能量代谢下降，并导致氧化损伤，而这种变化可通过 NAC 预处理来预防。
