Department of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, 4-24-1, Kuhonji, Kumamoto 862-0976, Japan.
J Toxicol Sci. 2011 Jun;36(3):253-9. doi: 10.2131/jts.36.253.
The involvement of oxidative stress has been suggested as a mechanism for toxicity caused by methylmercury (MeHg). One of the major critical sites for oxidative stress is the mitochondria. In this research, to clarify the target site in mitochondria affected by MeHg, the individual activities of the mitochondrial electron transport chain (ETC) (I∼IV) were examined in the liver, cerebrum and cerebellum of MeHg-intoxicated rats. In addition, to elucidate the mechanism underlying MeHg toxicity, cytochrome c release, caspase 3 activity and histological study were examined in the cerebrum and cerebellum. The cerebellum was found to be an exclusive tissue in which significant MeHg-induced alterations were observed. The complex II activity in the cerebellum mitochondria significantly decreased after MeHg exposure. Cytochrome c release from mitochondria increased only in the cerebellum by MeHg exposure. However, no significant alterations in caspase 3 activity or histological structure were found in brain tissues. These results suggest that MeHg acts on the constituents of complex II in the cerebellum, and induces mitochondrial dysfunction, leading to a release of cytochrome c from mitochondria. These events were considered to occur at the early stage of MeHg intoxication.
氧化应激的参与被认为是甲基汞（MeHg）引起毒性的一种机制。线粒体是氧化应激的主要关键部位之一。在这项研究中，为了阐明 MeHg 中毒大鼠肝脏、大脑和小脑中线粒体受影响的靶位，检查了线粒体电子传递链（ETC）（I∼IV）的各个活性。此外，为了阐明 MeHg 毒性的机制，还检查了大脑和小脑中线粒体细胞色素 c 释放、半胱天冬酶 3 活性和组织学研究。发现小脑是唯一观察到明显 MeHg 诱导改变的组织。小脑线粒体的复合物 II 活性在 MeHg 暴露后显著降低。只有 MeHg 暴露才会导致小脑中线粒体细胞色素 c 从线粒体释放增加。然而，在脑组织中未发现 caspase 3 活性或组织学结构的显著改变。这些结果表明，MeHg 作用于小脑复合物 II 的组成部分，诱导线粒体功能障碍，导致线粒体细胞色素 c 释放。这些事件被认为发生在 MeHg 中毒的早期阶段。
