Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA
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 in...
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| Format: | Article |
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Wiley
2012-01-01
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| Series: | Journal of Toxicology |
| Online Access: | http://dx.doi.org/10.1155/2012/373678 |
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| author | Martyn A. Sharpe Andrew D. Livingston David S. Baskin |
| author_facet | Martyn A. Sharpe Andrew D. Livingston David S. Baskin |
| author_sort | Martyn A. Sharpe |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0e771128df044d529c9dcc32aea9cea5 |
| institution | Kabale University |
| issn | 1687-8191 1687-8205 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Toxicology |
| spelling | doaj-art-0e771128df044d529c9dcc32aea9cea52025-08-20T03:54:29ZengWileyJournal of Toxicology1687-81911687-82052012-01-01201210.1155/2012/373678373678Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNAMartyn A. Sharpe0Andrew D. Livingston1David S. Baskin2Department of Neurosurgery, The Methodist Hospital, 6565 Fannin Street, Houston, TX 77030, USADepartment of Neurosurgery, The Methodist Hospital, 6565 Fannin Street, Houston, TX 77030, USADepartment of Neurosurgery, The Methodist Hospital, 6565 Fannin Street, Houston, TX 77030, USAThimerosal 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.http://dx.doi.org/10.1155/2012/373678 |
| spellingShingle | Martyn A. Sharpe Andrew D. Livingston David S. Baskin Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA Journal of Toxicology |
| title | Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA |
| title_full | Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA |
| title_fullStr | Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA |
| title_full_unstemmed | Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA |
| title_short | Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA |
| title_sort | thimerosal derived ethylmercury is a mitochondrial toxin in human astrocytes possible role of fenton chemistry in the oxidation and breakage of mtdna |
| url | http://dx.doi.org/10.1155/2012/373678 |
| work_keys_str_mv | AT martynasharpe thimerosalderivedethylmercuryisamitochondrialtoxininhumanastrocytespossibleroleoffentonchemistryintheoxidationandbreakageofmtdna AT andrewdlivingston thimerosalderivedethylmercuryisamitochondrialtoxininhumanastrocytespossibleroleoffentonchemistryintheoxidationandbreakageofmtdna AT davidsbaskin thimerosalderivedethylmercuryisamitochondrialtoxininhumanastrocytespossibleroleoffentonchemistryintheoxidationandbreakageofmtdna |