What does this research mean for the field?

Lead and cadmium exhibit synergistic accumulation in biological tissues, which is driven by the upregulation of specific metal-transporter genes including Dmt1, Zip8, and Zip14. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to understand the combined effects of lead and cadmium and how transporter genes mediate these effects in mice.

May 18, 2026BioMetals0 citationsOpen Access

Synergistic interaction between lead and cadmium via metal-transporter gene upregulation in mice

TZTingting ZhangHenan University of Technology WXWeiqin XingHenan University of Technology JIJames A. IppolitoThe Ohio State University

Key Points

This research aims to understand the combined effects of lead and cadmium and how transporter genes mediate these effects in mice.
Mice were given varying doses of lead (15, 30, 108 mg kg −1) and cadmium (1, 2, 3 mg kg −1) via feed.
Liver, kidney, and bone samples were analyzed for metal concentrations, and gene expression levels were measured using qRT-PCR.
The expression levels of Dmt1, Zip8, and Zip14 were quantified in the liver and kidney to assess their role in metal transport.
At 108 mg kg −1 Pb, increasing Cd doses led to significant increases in Pb concentrations in the kidney (10.6%), liver (60.2%), and bone (19.6%).
Transporter gene Zip8 expression in the kidney increased by 69.5% in response to Pb and Cd exposure, while Dmt1 and Zip14 levels in the liver increased by 79.0% and 85.6%, respectively.
At higher Cd doses (≥ 1 mg kg −1), Pb increased Cd concentrations, but no significant changes in transporter gene expression were observed in the kidney.

Abstract

Abstract This study investigated the potential synergistic interactions between Pb and Cd, and assessed the contribution of transporter gene expression to the synergism. Mice were administered varying doses of Pb (15, 30 and 108 mg kg −1 ) or Cd (1, 2 and 3 mg kg −1 ), or a combination of both in the feed. Liver, kidney and bone samples were analyzed for Cd, Pb, Cu, Mn, Zn and Fe concentrations. For treatments exhibiting synergistic effects, the relative expression levels of the divalent metal transporter 1 ( Dmt1 ), ZRT-IRE-like protein 8 ( Zip8 ) and Zip14 were quantified in the liver and kidney using Quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR). At 108 mg kg −1 Pb , increasing Cd doses from 0 to 1 mg kg −1 significantly increased Pb concentrations in the kidney, liver and bone by 10.6, 60.2 and 19.6%, respectively; concurrently, the relative expression of the Zip8 in the kidney increased by 69.5%, while Dmt1 and Zip14 expression in the liver increased by 79.0 and 85.6%, respectively. At Cd doses ≥ 1 mg kg −1 , increasing Pb rate resulted in elevated Cd concentrations in the kidney, liver and bone; however, no significant changes in transporter expression levels were observed in the kidney under these treatments, possibly due to the upregulation of transporter genes in the intestines. Results demonstrate that interactions between Pb and Cd can be synergistic, and upregulation of certain transporter genes were responsible for such synergism. These findings offer important insights for mitigating the health risks associated with heavy metal exposure in animal and humans.

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