Review Article

Zinc as a countermeasure for cadmium toxicity

Hai-tao Yu1,2,3, Juan Zhen1,2,3, Ji-yan Leng1, Lu Cai2,4,5, Hong-lei Ji1, Bradley B. Keller3,5,6
1 The First Hospital of Jilin University, Changchun 130021, China
2 Pediatric Research Institute, Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY 40202, USA
3 Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Louisville, KY 40202, USA
4 Department of Radiation Oncology, University of Louisville School of Medicine, Louisville, KY 40202, USA
5 Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA
6 Cincinnati Children’s Heart Institute, Greater Louisville and Western Kentucky Practice, Louisville, KY 40202, USA
Correspondence to: Hong-lei Ji: jihonglei@aliyun.com, Bradley B. Keller: brad.keller@cchmc.org,
DOI: 10.1038/s41401-020-0396-4
Received: 19 December 2019
Accepted: 15 March 2020
Advance online: 13 April 2020

Abstract

Cadmium (Cd) is an important environmental pollutant and long-term Cd exposure is closely related to autoimmune diseases, cancer, cardiovascular diseases (CVD), and hepatic dysfunction. Zinc (Zn) is an essential metal that plays key roles in protein structure, catalysis, and regulation of their function. Numerous studies have shown that Zn can reduce Cd toxicity; however, the underlying mechanisms have not been extensively explored. Preclinical studies have revealed direct competition for sarcolemmal uptake between these two metals. Multiple sarcolemmal transporters participate in Cd uptake, including Zn transporters, calcium channels, and DMT1 (divalent metal transporter 1). Zn also induces several protective mechanisms, including MT (metallothionein) induction and favorable redox homeostasis. This review summarizes current knowledge related to the role of Zn and metal transporters in reducing Cd toxicity and discusses potential future directions of related research.
Keywords: cadmium; metallothionein; Zinc; Zinc transporters

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