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10.3390/w15030448
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Article

Arsenite Methyltransferase Is an Important Mediator of Hematotoxicity Induced by Arsenic in Drinking Water

by
Sebastian Medina
1,2,*,
Haikun Zhang
1,
Laura V. Santos-Medina
2,
Zachary A. Yee
2,
Kaitlin J. Martin
2,
Guanghua Wan
1,
Alicia M. Bolt
1,
Xixi Zhou
1,
Miroslav Stýblo
3 and
Ke Jian Liu
1,4
1
Department of Pharmaceutical Sciences, The University of New Mexico College of Pharmacy, Albuquerque, NM 87131, USA
2
Department of Biology, New Mexico Highlands University, Las Vegas, NM 87701, USA
3
Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
4
Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA
*
Author to whom correspondence should be addressed.
Water 2023, 15(3), 448; https://doi.org/10.3390/w15030448
Submission received: 31 October 2022 / Revised: 10 January 2023 / Accepted: 19 January 2023 / Published: 22 January 2023
(This article belongs to the Special Issue Arsenic in Drinking Water and Human Health)
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Abstract

Chronic arsenic exposures via the consumption of contaminated drinking water are clearly associated with many deleterious health outcomes, including anemia. Following exposure, trivalent inorganic arsenic (AsIII) is methylated through a series of arsenic (+III oxidation state) methyltransferase (As3MT)-dependent reactions, resulting in the production of several intermediates with greater toxicity than the parent inorganic arsenicals. The extent to which inorganic vs. methylated arsenicals contribute to AsIII-induced hematotoxicity remains unknown. In this study, the contribution of As3MT-dependent biotransformation to the development of anemia was evaluated in male As3mt-knockout (KO) and wild-type, C57BL/6J, mice following 60-day drinking water exposures to 1 mg/L (ppm) AsIII. The evaluation of hematological indicators of anemia revealed significant reductions in red blood cell counts, hemoglobin levels, and hematocrit in AsIII-exposed wild-type mice as compared to unexposed controls. No such changes in the blood of As3mt-KO mice were detected. Compared with unexposed controls, the percentages of mature RBCs in the bone marrow and spleen (measured by flow cytometry) were significantly reduced in the bone marrow of AsIII-exposed wild-type, but not As3mt-KO mice. This was accompanied by increased levels of mature RBCS in the spleen and elevated levels of circulating erythropoietin in the serum of AsIII-exposed wild-type, but not As3mt-KO mice. Taken together, the findings from the present study suggest that As3MT-dependent biotransformation has an essential role in mediating the hematotoxicity of AsIII following drinking water exposures.
Keywords: arsenic; arsenite (AsIII); anemia; red blood cells; biotransformation; arsenic (+III oxidation state) methyltransferase (As3MT) arsenic; arsenite (AsIII); anemia; red blood cells; biotransformation; arsenic (+III oxidation state) methyltransferase (As3MT)

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MDPI and ACS Style

Medina, S.; Zhang, H.; Santos-Medina, L.V.; Yee, Z.A.; Martin, K.J.; Wan, G.; Bolt, A.M.; Zhou, X.; Stýblo, M.; Liu, K.J. Arsenite Methyltransferase Is an Important Mediator of Hematotoxicity Induced by Arsenic in Drinking Water. Water 2023, 15, 448. https://doi.org/10.3390/w15030448

AMA Style

Medina S, Zhang H, Santos-Medina LV, Yee ZA, Martin KJ, Wan G, Bolt AM, Zhou X, Stýblo M, Liu KJ. Arsenite Methyltransferase Is an Important Mediator of Hematotoxicity Induced by Arsenic in Drinking Water. Water. 2023; 15(3):448. https://doi.org/10.3390/w15030448

Chicago/Turabian Style

Medina, Sebastian, Haikun Zhang, Laura V. Santos-Medina, Zachary A. Yee, Kaitlin J. Martin, Guanghua Wan, Alicia M. Bolt, Xixi Zhou, Miroslav Stýblo, and Ke Jian Liu. 2023. "Arsenite Methyltransferase Is an Important Mediator of Hematotoxicity Induced by Arsenic in Drinking Water" Water 15, no. 3: 448. https://doi.org/10.3390/w15030448

APA Style

Medina, S., Zhang, H., Santos-Medina, L. V., Yee, Z. A., Martin, K. J., Wan, G., Bolt, A. M., Zhou, X., Stýblo, M., & Liu, K. J. (2023). Arsenite Methyltransferase Is an Important Mediator of Hematotoxicity Induced by Arsenic in Drinking Water. Water, 15(3), 448. https://doi.org/10.3390/w15030448

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