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Zinc Deficiency and Arsenic Exposure Can Act Both Independently or Cooperatively to Affect Zinc Status, Oxidative Stress, and Inflammatory Response

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Abstract

The negative health impact of zinc deficiency overlaps significantly with arsenic exposure, and is associated with increased risk for chronic diseases. Arsenic contamination in the groundwater often co-exists in regions of the world that are prone to zinc deficiency. Notably, low zinc status shares many hallmarks of arsenic exposure, including increased oxidative stress and inflammation. Despite their common targets and frequent co-distribution in the population, little is known regarding the interaction between zinc deficiency and arsenic exposure. In this study, we tested the effect of arsenic exposure at environmentally relevant doses in combination with a physiologically relevant level of zinc deficiency (marginal zinc deficiency) on zinc status, oxidative damage, and inflammation. In cell culture, zinc-deficient THP-1 monocytes co-exposed with arsenic resulted in further reduction in intracellular zinc, as well as further increase in oxidative stress and inflammatory markers. In an animal study, zinc-deficient mice had further decrease in zinc status when co-exposed to arsenic. Zinc deficiency, but not arsenic exposure, resulted in an increase in baseline transcript abundance of inflammatory markers in the liver. Upon lipopolysaccharide challenge to elicit an acute inflammatory response, arsenic exposure, but not zinc deficiency, resulted in an increase in proinflammatory response. In summary, zinc deficiency and arsenic exposure can function independently or cooperatively to affect zinc status, oxidant stress, and proinflammatory response. The results highlight the need to consider both nutritional status and arsenic exposures together when considering their impact on health outcomes in susceptible populations.

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Abbreviations

Rn18S:

18S ribosomal RNA

CAT:

Catalase

CCL2:

C-C motif chemokine ligand 2

CXCL8:

C-X-C motif chemokine ligand 8

H2DCFDA:

2′,7′-Dichlorodihydrofluorescein diacetate

DCF:

2′,7′-Dichlorofluorescein

EAR:

Estimated average requirement

FBS:

Fetal bovine serum

FluoZin-3:

FluoZin-3 acetoxymethyl ester

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

HMOX1:

Heme oxygenase I

ICAM1:

Intercellular adhesion molecule 1

ICP-OES:

Inductively coupled plasma optical emission spectrometry

IL6:

Interleukin-6

IL8:

Interleukin-8

LPS:

Lipopolysaccharide

MZD:

Marginally zinc deficient

MFI:

Mean fluorescence intensity

MT:

Metallothionein

PARP-1:

Poly (ADP-ribose) polymerase-1

ROS:

Reactive oxygen species

SOD1:

Superoxide dismutase-1

WHO:

World Health Organization

ZA:

Zinc adequate

As:

Sodium arsenite

ZD:

Zinc deficient

PBS:

Phosphate-buffered saline

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Acknowledgements

We thank Dr. Adam Branscum for providing consultation and advice regarding statistical analyses. We also acknowledge the technical support provided by Dr. Jodi Schilz and Karen Simmons.

Funding

This work was supported by the National Institutes of Health (NIH) Competing Revision to 1R01ES021100 NIH Revision Awards for Creating Virtual Consortium for Translational/Transdisciplinary Environmental Research (ViCTER) (R01), as well as the Oregon Agricultural Experimental Station (EH) and the National Institute of Environmental Health Sciences (NIEHS) supported Environmental Health Sciences Center Grant (P30 ES000210). Training support for Dr. Dashner was provided by the 5K12GM088021-08 Academic Science Education and Research Training (ASERT) Program.

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Author notes

  1. Carmen P. Wong and Erica J. Dashner-Titus contributed equally to this work.

Authors and Affiliations

  1. School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331, USA

    Carmen P. Wong, Tyler T. Chase & Emily Ho

  2. Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA

    Erica J. Dashner-Titus, Sandra C. Alvarez & Laurie G. Hudson

  3. Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA

    Emily Ho

  4. Moore Family Center for Whole Grain Foods, Nutrition and Preventive Health, Oregon State University, Corvallis, OR, 97331, USA

    Emily Ho

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  1. Carmen P. Wong
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Correspondence to Emily Ho.

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Wong, C.P., Dashner-Titus, E.J., Alvarez, S.C. et al. Zinc Deficiency and Arsenic Exposure Can Act Both Independently or Cooperatively to Affect Zinc Status, Oxidative Stress, and Inflammatory Response. Biol Trace Elem Res 191, 370–381 (2019). https://doi.org/10.1007/s12011-019-1631-z

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