Fluoride-induced oxidative stress is involved in the morphological damage and dysfunction of liver in female mice.
Fluoride-induced oxidative stress is involved in the morphological damage and dysfunction of liver in female mice.
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DOI：
10.1016/j.chemosphere.2015.08.030
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发表时间：
2015-11
期刊：
影响因子：
8.8
通讯作者：
Bian-hua Zhou;J. Zhao;Jeffrey Liu;Ji-liang Zhang;Jian Li;Hong-wei Wang
中科院分区：
文献类型：
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作者：
Bian-hua Zhou;J. Zhao;Jeffrey Liu;Ji-liang Zhang;Jian Li;Hong-wei Wang
氟是环境和工业中毒性最大的污染物之一，具有肝毒性。氧化应激对肝脏氟耐受性的影响尚不清楚。本研究分别采用苏木素伊红染色和透射电子显微镜（TEM）观察肝脏的形态学和超微结构特征。氧化应激参与分析和过氧化氢酶（Cat），谷胱甘肽过氧化物酶1（GSH-Px 1），一氧化氮合酶2（NOS 2），超氧化物歧化酶1（SOD 1）的mRNA表达水平进行了研究通过实时PCR。还检测到肝功能参数的变化。结果表明，氟处理70 d后，肝脏和血清中活性氧含量显著升高，SOD、GSH-Px活性和总抗氧化能力（T-AOC）显著降低，一氧化氮（NO）和丙二醛（MDA）含量显著升高。F处理70 d后，Cat、GSH-Px 1和SOD的mRNA表达水平显著下调，而NOS 2的mRNA表达水平显著上调。光学显微镜还显示肝细胞融合成碎片;细胞边界不清楚，细胞核轻度染色。TEM进一步显示肝细胞的特征为模糊的核膜和线粒体膜、扩张的内质网和加重的空泡变性。血清谷丙转氨酶、谷草转氨酶、碱性磷酸酶、乳酸脱氢酶活性及总胆红素水平升高。总之，这些结果表明，F干扰了抗氧化酶活性的平衡和肝脏的形态学变化，这参与了小鼠肝脏功能障碍。
Fluoride (F), one of the most toxic environmental and industrial pollutants, is known to exert hepatotoxicity. The contribution of oxidative stress to the F tolerance of liver remains largely unknown. In this study, the morphological and ultrastructural characteristics of liver were observed using hematoxylin and eosin staining and transmission electron microscopy (TEM), respectively. Oxidative-stress participations was analysed and the mRNA expression levels of catalase (Cat), glutathione peroxidase 1 (GSH-Px1), nitric oxide synthase 2 (NOS2), and superoxide dismutase 1 (SOD1) were investigated by real-time PCR. Changes in liver-function parameters were also detected. Results showed that the reactive content of reactive oxygen species increased significantly, whereas SOD and GSH-Px activities, as well as total anti-oxidising capability (T-AOC), decreased significantly, with increased nitric oxide (NO) and malondialdehyde (MDA) contents in liver and serum after 70 days of F treatment. The mRNA expression levels of Cat, GSH-Px1, and SOD were significantly downregulated, whereas NOS2 mRNA expression level was up upregulated, after F treatment for 70 days. Light microscopy also revealed that hepatocytes were fused into pieces; cell boundaries were unclear, and nuclei were lightly stained. TEM further showed that hepatocytes were characterised by vague nuclear and mitochondrial membranes, dilated endoplasmic reticulum, and aggravated vacuolar degeneration. Activities of alanine transaminase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase, as well as the level of total bilirubin in serum increased. Overall, these results indicated that F interfered with the balance of antioxidase activity and morphological changes in liver, which were involved in mouse liver dysfunction.