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

International Journal of Molecular Sciences

Jean-Paul Bourdineaud²  Muriel Laclau²  Régine Maury-Brachet²  Patrice Gonzalez²  Magalie Baudrimont²  Nathalie Mesmer-Dudons²  Masatake Fujimura¹  Aline Marighetto⁴  David Godefroy³  William Rostène³ 

[1] National Institute for Minamata Disease, Pathology Section, Department of Basic Medical Sciences, 4058-18 Hama, Minamata, Kumamoto 867-0008, Japan; E-Mail:;Bordeaux University-CNRS, UMR EPOC 5805, Arcachon Marine Station, Place du Docteur Peyneau, Arcachon, 33120, France; E-Mails:;Institut de la Vision, UMRS 968, INSERM-University Pierre et Marie Curie, 17 Rue Moreau, Paris, 75012, France; E-Mails:;Laboratoire de Neurosciences Cognitives, Bordeaux University-CNRS UMR 5106, Avenue des Facultés, Talence, 33405, France; E-Mail:

关键词: methylmercury;    fish consumption;    chemokine;    mercury accumulation;    metallothionein;    demethylation;   

DOI  :  10.3390/ijms13067710

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.