Abstract：
Heavy metal exposure leads to multiple system dysfunctions. The mechanisms are likely multifactorial and involve inflammation and oxidative stress. The aim of this study was to evaluate markers and risk factors for atherosclerosis in the LDL receptor knockout mouse model chronically exposed to inorganic mercury (Hg) in the drinking water. Results revealed that Hg exposed mice present increased plasma levels of cholesterol, without alterations in glucose. As a major source and target of oxidants, we evaluated mitochondrial function. We found that liver mitochondria from Hg treated mice show worse respiratory control, lower oxidative phosphorylation efficiency and increased H2O2 release. In addition, Hg induced mitochondrial membrane permeability transition. Erythrocytes from Hg treated mice showed a 50% reduction in their ability to take up oxygen, lower levels of reduced glutathione (GSH) and of antioxidant enzymes (SOD, catalase and GPx). The Hg treatment disturbed immune system cells counting and function. While lymphocytes were reduced, monocytes, eosinophils and neutrophils were increased. Peritoneal macrophages from Hg treated mice showed increased phagocytic activity. Hg exposed mice tissues present metal impregnation and parenchymal architecture alterations. In agreement, increased systemic markers of liver and kidney dysfunction were observed. Plasma, liver and kidney oxidative damage indicators (MDA and carbonyl) were increased while GSH and thiol groups were diminished by Hg exposure. Importantly, atherosclerotic lesion size in the aorta root of Hg exposed mice were larger than in controls. In conclusion, in vivo chronic exposure to Hg worsens the hypercholesterolemia, impairs mitochondrial bioenergetics and redox function, alters immune cells profile and function, causes several tissues oxidative damage and accelerates atherosclerosis development.
摘要：
重金属暴露导致多个系统功能障碍。机制可能是多因素的，涉及炎症和氧化应激。这项研究的目的是评估长期暴露于饮用水中无机汞（Hg）的LDL受体敲除小鼠模型中动脉粥样硬化的标志物和危险因素。结果显示，汞暴露小鼠血浆胆固醇水平升高，没有葡萄糖的改变。作为氧化剂的主要来源和目标，我们评估了线粒体功能。我们发现汞处理小鼠的肝脏线粒体表现出较差的呼吸控制，降低氧化磷酸化效率和增加H2O2释放。此外,Hg诱导线粒体膜通透性转变。汞处理小鼠的红细胞吸收氧气的能力降低了50％，较低水平的还原型谷胱甘肽(GSH)和抗氧化酶(SOD，过氧化氢酶和GPx）。Hg处理扰乱了免疫系统细胞计数和功能。当淋巴细胞减少时，单核细胞,嗜酸性粒细胞和中性粒细胞增加。来自Hg处理的小鼠的腹膜巨噬细胞显示出增加的吞噬活性。暴露于汞的小鼠组织存在金属浸渍和实质结构改变。在协议中,观察到肝脏和肾脏功能障碍的全身标志物增加。血浆,肝脏和肾脏氧化损伤指标（MDA和羰基）增加，而GSH和巯基减少汞暴露。重要的是,Hg暴露小鼠主动脉根部的动脉粥样硬化病变大小大于对照组。总之,体内长期接触汞会使高胆固醇血症恶化，损害线粒体生物能学和氧化还原功能，改变免疫细胞的轮廓和功能，引起几种组织的氧化损伤并加速动脉粥样硬化的发展。
