Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin
Journal of Toxicology Volume 2012 (2012), Article ID 373678, 12 pages http://dx.doi.org/10.1155/2012/373678
Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA
Department of Neurosurgery, The Methodist Hospital, 6565 Fannin Street, Houston, TX 77030, USA
Received 26 March 2012; Revised 7 May 2012; Accepted 21 May 2012
Academic Editor: Y. James Kang
Copyright © 2012 Martyn A. Sharpe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Thimerosal generates ethylmercury in aqueous solution and is widely used as preservative. We have investigated the toxicology of Thimerosal in normal human astrocytes, paying particular attention to mitochondrial function and the generation of specific oxidants. We find that ethylmercury not only inhibits mitochondrial respiration leading to a drop in the steady state membrane potential, but also concurrent with these phenomena increases the formation of superoxide, hydrogen peroxide, and Fenton/Haber-Weiss generated hydroxyl radical. These oxidants increase the levels of cellular aldehyde/ketones. Additionally, we find a five-fold increase in the levels of oxidant damaged mitochondrial DNA bases and increases in the levels of mtDNA nicks and blunt-ended breaks. Highly damaged mitochondria are characterized by having very low membrane potentials, increased superoxide/hydrogen peroxide production, and extensively damaged mtDNA and proteins. These mitochondria appear to have undergone a permeability transition, an observation supported by the five-fold increase in Caspase-3 activity observed after Thimerosal treatment.
1.1. Thimerosal and Ethylmercury
Thimerosal is a preservative that is widely used in medical products, including as a preservative in vaccines, immunoglobulin preparations, skin test antigens, antivenins, ophthalmic and nasal products, and tattoo inks, and is composed of 49.6 percent ethylmercury by weight . The widespread use of Thimerosal exposes many to its potential toxic effects, especially
𝑛 𝑢 𝑡 𝑒 𝑟 𝑜 and in neonates. We report the results of a series of experiments using cultured normal human astrocytes (NHA) exposed to Thimerosal to study the compound’s effect on astrocyte mitochondria.
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