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

  • Carmen P. Wong
  • Erica J. Dashner-Titus
  • Sandra C. Alvarez
  • Tyler T. Chase
  • Laurie G. Hudson
  • Emily HoEmail author
Article
  • 78 Downloads

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.

Keywords

Arsenic Zinc Oxidative stress Inflammation 

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

Notes

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 Information

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.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

Supplementary material

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Figure S1 (PDF 115 kb)
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Table S1 (DOCX 15.1 kb)

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Authors and Affiliations

  1. 1.School of Biological and Population Health SciencesOregon State UniversityCorvallisUSA
  2. 2.Department of Pharmaceutical Sciences, College of PharmacyUniversity of New Mexico Health Sciences CenterAlbuquerqueUSA
  3. 3.Linus Pauling InstituteOregon State UniversityCorvallisUSA
  4. 4.Moore Family Center for Whole Grain Foods, Nutrition and Preventive HealthOregon State UniversityCorvallisUSA

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