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
IJMS. 2012-06-21; 13(6): 7710-7738
Lire sur PubMed
1. Int J Mol Sci. 2012;13(6):7710-38. doi: 10.3390/ijms13067710. Epub 2012 Jun 21.
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.
Bourdineaud JP(1), Laclau M, Maury-Brachet R, Gonzalez P, Baudrimont M,
Mesmer-Dudons N, Fujimura M, Marighetto A, Godefroy D, Rostène W, Brèthes D.
(1)Bordeaux University-CNRS, UMR EPOC 5805, Arcachon Marine Station, Place du
Docteur Peyneau, Arcachon, 33120, France; E-Mails:
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.
PMID: 22837723 [Indexed for MEDLINE]