TitleZinc supplementation alters tissue distribution of arsenic in Mus musculus.
Publication TypeJournal Article
Year of Publication2023
AuthorsDashner-Titus, EJ, Schilz, JR, Alvarez, SA, Wong, CP, Simmons, K, Ho, E, Hudson, LG
JournalToxicol Appl Pharmacol
Date Published2023 Nov 01
KeywordsAnimals, Arsenic, Arsenites, Dietary Supplements, Humans, Mice, Tissue Distribution, Zinc

Arsenic occurs naturally in the environment and humans can be exposed through food, drinking water and inhalation of air-borne particles. Arsenic exposure is associated with cardiovascular, pulmonary, renal, immunologic, and developmental toxicities as well as carcinogenesis. Arsenic displays dose-depen toxicities in target organs or tissues with elevated levels of arsenic. Zinc is an essential micronutrient with proposed protective benefits due to its antioxidant properties, integration into zinc-containing proteins and zinc-related immune signaling. In this study, we tested levels of arsenic and zinc in plasma, kidney, liver, and spleen as model tissues after chronic (42-day) treatment with either arsenite, zinc, or in combination. Arsenite exposure had minimal impact on tissue zinc levels with the exception of the kidney. Conversely, zinc supplementation of arsenite-exposed mice reduced the amount of arsenic detected in all tissues tested. Expression of transporters associated with zinc or arsenic influx and efflux were evaluated under each treatment condition. Significant effects of arsenite exposure on zinc transporter expression displayed tissue selectivity for liver and kidney, and was restricted to Zip10 and Zip14, respectively. Arsenite also interacted with zinc co-exposure for Zip10 expression in liver tissue. Pairwise comparisons show neither arsenite nor zinc supplementation alone significantly altered expression of transporters utilized by arsenic. However, significant interactions between arsenite and zinc were evident for Aqp7 and Mrp1 in a tissue selective manner. These findings illustrate interactions between arsenite and zinc leading to changes in tissue metal level and suggest a potential mechanism by which zinc may offer protection from arsenic toxicities.

Alternate JournalToxicol Appl Pharmacol
PubMed ID37797845
PubMed Central IDPMC10729601
Grant ListP50 ES026102 / ES / NIEHS NIH HHS / United States
P42 ES025589 / ES / NIEHS NIH HHS / United States
P30 CA118100 / CA / NCI NIH HHS / United States
R25 HG007630 / HG / NHGRI NIH HHS / United States
P30 ES030287 / ES / NIEHS NIH HHS / United States
R836157 / EPA / EPA / United States
R01 ES021100 / ES / NIEHS NIH HHS / United States
K12 GM088021 / GM / NIGMS NIH HHS / United States