Effects of methylmercury contained in a diet mimicking the Wayana Amerindians contamination through fish consumption: mercury accumulation, metallothionein induction, gene expression variations, and role of the chemokine CCL2.
Effects of methylmercury contained in a diet mimicking the Wayana Amerindians contamination through fish consumption: mercury accumulation, metallothionein induction, gene expression variations, and role of the chemokine CCL2.
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DOI：
10.3390/ijms13067710
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发表时间：
2012
影响因子：
5.6
通讯作者：
Brèthes D
中科院分区：
文献类型：
--
作者：
Bourdineaud JP;Laclau M;Maury-Brachet R;Gonzalez P;Baudrimont M;Mesmer-Dudons N;Fujimura M;Marighetto A;Godefroy D;Rostène W;Brèthes D
甲基汞（MeHg）是一种强烈的神经毒素，人类主要通过食用鱼类接触这种污染物。我们解决了这样一个问题，即模仿法属圭亚那的Wayanas美洲印第安人的鱼类消费的饮食是否会导致小鼠出现可观察到的不良反应。圭亚那成年男子平均汞剂量为7克汞/周/公斤体重。我们决定用0.1%的冻干Hoplias aimara鱼补充素食小鼠饮食，Wayanas人喜欢这种鱼，相当于Wayanas美洲印第安人的剂量。对照组和aimara组食物颗粒的总汞含量分别为1.4 ± 0.2和5.4 ± 0.5 ng Hg/g。暴露14个月后，以干重计，身体部位和组织中汞浓度最高的是毛发（733纳克/克）和肾脏（511纳克/克），其次是肝脏（77纳克/克）。令人惊讶的是，尽管甲基汞是一种神经毒性化合物，但大脑中汞的积累水平很低（皮层中为35纳克/克）。金属硫蛋白（MT）的蛋白质浓度增加，仅在这些组织（肾脏，肌肉），其中甲基汞去甲基化发生。这可以被认为是二价汞污染的分子标志，因为只有Hg 2+被报道在污染的组织中诱导MT积累。在相应的敲除（KO）小鼠中，趋化因子CCL 2的合成受到抑制，导致肝脏和大脑中基因表达模式发生重要变化。在暴露于含aimara的饮食三个月后，10个基因中的8个（Sdhb，Cytb，Cox 1，Sod 1，Sod 2，Mt 2，Mdr 1a和Bax）在野生型小鼠肝脏中受到抑制，而在KO Ccl 2 −/−小鼠中没有差异表达。在野生型小鼠大脑中，12个基因中的6个（Cytb，Cox 1，Sod 1，Sod 2，Mdr 1a和Bax）呈现刺激表达，而在KO Ccl 2 −/−小鼠中所有基因的表达均保持在基础水平。在艾马拉喂养的小鼠的肝脏中，观察到组织学变化的累积汞浓度低至32纳克/克，dw，和金属沉积物内观察到肝细胞的细胞质。
Methylmercury (MeHg) is a potent neurotoxin, and human beings are mainly exposed to this pollutant through fish consumption. We addressed the question of whether a diet mimicking the fish consumption of Wayanas Amerindians from French Guiana could result in observable adverse effects in mice. Wayanas adult men are subjected to a mean mercurial dose of 7 g Hg/week/kg of body weight. We decided to supplement a vegetarian-based mice diet with 0.1% of lyophilized Hoplias aimara fish, which Wayanas are fond of and equivalent to the same dose as that afflicting the Wayanas Amerindians. Total mercury contents were 1.4 ± 0.2 and 5.4 ± 0.5 ng Hg/g of food pellets for the control and aimara diets, respectively. After 14 months of exposure, the body parts and tissues displaying the highest mercury concentration on a dry weight (dw) basis were hair (733 ng/g) and kidney (511 ng/g), followed by the liver (77 ng/g). Surprisingly, despite the fact that MeHg is a neurotoxic compound, the brain accumulated low levels of mercury (35 ng/g in the cortex). The metallothionein (MT) protein concentration only increased in those tissues (kidney, muscles) in which MeHg demethylation had occurred. This can be taken as a molecular sign of divalent mercurial contamination since only Hg2+ has been reported yet to induce MT accumulation in contaminated tissues. The suppression of the synthesis of the chemokine CCL2 in the corresponding knockout (KO) mice resulted in important changes in gene expression patterns in the liver and brain. After three months of exposure to an aimara-containing diet, eight of 10 genes selected (Sdhb, Cytb, Cox1, Sod1, Sod2, Mt2, Mdr1a and Bax) were repressed in wild-type mice liver whereas none presented a differential expression in KO Ccl2−/− mice. In the wild-type mice brain, six of 12 genes selected (Cytb, Cox1, Sod1, Sod2, Mdr1a and Bax) presented a stimulated expression, whereas all remained at the basal level of expression in KO Ccl2−/− mice. In the liver of aimara-fed mice, histological alterations were observed for an accumulated mercury concentration as low as 32 ng/g, dw, and metal deposits were observed within the cytoplasm of hepatic cells.
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DOI：
10.1111/j.1600-0773.1993.tb01563.x
发表时间：
1993-10-01
期刊：
PHARMACOLOGY & TOXICOLOGY
影响因子：
--
作者：
ANDERSEN, HR;ANDERSEN, O
通讯作者：
ANDERSEN, O
影响因子：
3.5
作者：
Huang, Chun-Fa;Hsu, Chuan-Jen;Lin-Shiau, Shoei-Yn
通讯作者：
Lin-Shiau, Shoei-Yn
影响因子：
6.8
作者：
Grotto, Denise;Vicentini, Juliana;Barbosa, Fernando, Jr.
通讯作者：
Barbosa, Fernando, Jr.
影响因子：
2.2
作者：
Desaulniers, Daniel;Xiao, Gong-hua;Bowers, Wayne J.
通讯作者：
Bowers, Wayne J.
影响因子：
6.4
作者：
Dagouassat, Maylis;Suffee, Nadine;Charnaux, Nathalie
通讯作者：
Charnaux, Nathalie