title: 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.
abstract: 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 Hg(2+) 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.
authors: Bordeaux University-CNRS, UMR EPOC 5805, Arcachon Marine Station, Place du Docteur Peyneau, Arcachon, 33120, France.
authors: Jean-Paul
authors: JP
authors: Bourdineaud
authors: Bordeaux University-CNRS, UMR EPOC 5805, Arcachon Marine Station, Place du Docteur Peyneau, Arcachon, 33120, France.
authors: Muriel
authors: M
authors: Laclau
authors: Bordeaux University-CNRS, UMR EPOC 5805, Arcachon Marine Station, Place du Docteur Peyneau, Arcachon, 33120, France.
authors: Régine
authors: R
authors: Maury-Brachet
authors: Bordeaux University-CNRS, UMR EPOC 5805, Arcachon Marine Station, Place du Docteur Peyneau, Arcachon, 33120, France.
authors: Patrice
authors: P
authors: Gonzalez
authors: Bordeaux University-CNRS, UMR EPOC 5805, Arcachon Marine Station, Place du Docteur Peyneau, Arcachon, 33120, France.
authors: Magalie
authors: M
authors: Baudrimont
authors: Bordeaux University-CNRS, UMR EPOC 5805, Arcachon Marine Station, Place du Docteur Peyneau, Arcachon, 33120, France.
authors: Nathalie
authors: N
authors: Mesmer-Dudons
authors: National Institute for Minamata Disease, Pathology Section, Department of Basic Medical Sciences, 4058-18 Hama, Minamata, Kumamoto 867-0008, Japan.
authors: Masatake
authors: M
authors: Fujimura
authors: Laboratoire de Neurosciences Cognitives, Bordeaux University-CNRS UMR 5106, Avenue des Facultés, Talence, 33405, France.
authors: Aline
authors: A
authors: Marighetto
authors: Institut de la Vision, UMRS 968, INSERM-University Pierre et Marie Curie, 17 Rue Moreau, Paris, 75012, France.
authors: David
authors: D
authors: Godefroy
authors: Institut de la Vision, UMRS 968, INSERM-University Pierre et Marie Curie, 17 Rue Moreau, Paris, 75012, France.
authors: William
authors: W
authors: Rostène
authors: Institut de Biochimie et Génétique Cellulaires, UMR 5095 CNRS-Bordeaux University, 1 rue Camille Saint-Saëns, Bordeaux, 33077 Cedex, France.
authors: Daniel
authors: D
authors: Brèthes
mesh_terms: D000328:Adult; D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D005396:Fish Products / Q000009:adverse effects*; D005506:Food Contamination; D005616:French Guiana; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis*; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D008767:Methylmercury Compounds; D008668:Metallothionein; C004925:methylmercuric chloride