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Decreased plasma thiol antioxidant barrier and selenoproteins as potential biomarkers for ongoing methylmercury intoxication and an individual protective capacity

  • Molecular Toxicology
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Abstract

Manifestation of methylmercury (MeHg) toxicity depends on individual susceptibility to MeHg, as well as MeHg burden level. Therefore, biomarkers that reflect the protective capacity against MeHg are needed. The critical role of oxidative stress in the pathogenesis of MeHg cytotoxicity has been demonstrated. Because MeHg has high affinity for selenohydryl groups, sulfhydryl groups, and selenides, and causes posttranscriptional defects in selenoenzymes, proteins with selenohydryl and sulfhydryl groups should play a critical role in mediating MeHg-induced oxidative stress. Here, plasma oxidative stress markers and selenoproteins were investigated in MeHg-intoxicated rats showing neuropathological changes after 4 weeks of MeHg exposure. The thiol antioxidant barrier (–SHp) level significantly decreased 2 weeks after MeHg exposure, which is an early stage at which no systemic oxidative stress, histopathological changes, or clinical signs were detected. Diacron reactive oxidant metabolite (d-ROM) levels significantly increased 3 weeks after MeHg exposure, indicating the occurrence of systemic oxidative stress. Rats treated with lead acetate or cadmium chloride showed no changes in levels of –SHp and d-ROM. Selenoprotein P1 abundance significantly decreased in MeHg-treated rats, whereas it significantly increased in rats treated with Pb or Cd. Plasma selenium-dependent glutathione peroxidase (GPx3) activity also significantly decreased after MeHg exposure, whereas plasma non-selenoenzyme glutathione reductase activity significantly increased in MeHg-treated rats. The results suggest that decreased capacity of –SHp and selenoproteins (GPx3 and selenoprotein P) can be useful biomarkers of ongoing MeHg cytotoxicity and the individual protective capacity against the MeHg body burden.

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Acknowledgments

This work was partly supported by the Japan Society for the Promotion of Science KAKENHI (Grant No. 25460402). The authors thank Ms. Kyoko Yoshihara, Ayumi Onitsuka, Eri Kawano, Michiko Fuchigami, and Miwa Matsunaga for excellent technical assistance.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Clinical Medicine, National Institute for Minamata Disease, 4058-18 Hama, Minamata, 867-0008, Japan

    Fusako Usuki

  2. Department of Basic Medical Sciences, National Institute for Minamata Disease, 4058-18 Hama, Minamata, 867-0008, Japan

    Masatake Fujimura

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  1. Fusako Usuki
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  2. Masatake Fujimura
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Correspondence to Fusako Usuki.

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Usuki, F., Fujimura, M. Decreased plasma thiol antioxidant barrier and selenoproteins as potential biomarkers for ongoing methylmercury intoxication and an individual protective capacity. Arch Toxicol 90, 917–926 (2016). https://doi.org/10.1007/s00204-015-1528-3

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  • DOI: https://doi.org/10.1007/s00204-015-1528-3

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