Mercury-Induced Toxicity: Multiple Mechanisms of Action

In: de Voogt, P. (eds) Reviews of Environmental Contamination and Toxicology, vol 240. Springer, Cham. https://doi.org/10.1007/398_2016_1

Alkyl Mercury-Induced Toxicity: Multiple Mechanisms of Action

Risher JF, Tucker P. Division of Toxicology and Human Health Sciences, Agency for Toxic Substances and Disease Registry, US Centers for Disease Control and Prevention, 1600 Clifton Road (MS F-58), Atlanta, GA, 30333, USA.

Abstract

There are a number of mechanisms by which alkylmercury compounds cause toxic action in the body. Collectively, published studies reveal that there are some similarities between the mechanisms of the toxic action of the mono-alkyl mercury compounds methylmercury (MeHg) and ethylmercury (EtHg). This paper represents a summary of some of the studies regarding these mechanisms of action in order to facilitate the understanding of the many varied effects of alkylmercurials in the human body. The similarities in mechanisms of toxicity for MeHg and EtHg are presented and compared. The difference in manifested toxicity of MeHg and EtHg are likely the result of the differences in exposure, metabolism, and elimination from the body, rather than differences in mechanisms of action between the two.

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Summary and Conclusions

There are many commonalities/similarities in the mechanisms of toxic action of methylmercury and ethylmercury (from thimerosal)… Evidence for the similarity of the various mechanisms of toxicity include the following:

• Both MeHg and EtHg bind to the amino acid cysteine (Clarkson 1995; Wu et al. 2008)…

• Both decrease glutathione activity, thus providing less protection from the oxidative stress caused by MeHg and EtHg (Carocci et al. 2014; Ndountse and Chan (2008); Choi et al. 1996; Franco et al. 2006; Mori et al. 2007; Muller et al. 2001; Ndountse and Chan 2008; Wu et al. 2008)…

• Both disrupt glutamate homeostasis (Farina et al. 2003a, b; Manfroi et al. 2004; Mutkus et al. 2005; Yin et al. 2007).

• Both cause oxidative stress/creation of ROS (Dreiem and Seegal 2007; Garg and Chang 2006; Myhre et al. 2003; Sharpe et al. 2012; Yin et al. 2007)…

• Both cause effects on receptor binding/neurotransmitter release involving one or more transmitters (Basu et al. 2008; Coccini et al. 2000; Cooper et al. 2003; Fonfria et al. 2001; Ida-Eto et al. 2011; Ndountse and Chan 2008; Yuan and Atchison 2003).

• Both cause DNA damage or impair DNA synthesis (Burke et al. 2006; Sharpe et al. 2012; Wu et al. 2008).