Cadmium induces iron deficiency anemia through the suppression of iron transport in the duodenum.

Abstract

Cadmium (Cd) is an environmental contaminant that triggers toxic effects in various tissues such as the kidney, liver, and lung. Cd can also cause abnormal iron metabolism, leading to anemia. Iron homeostasis is regulated by intestinal absorption. However, whether Cd affects the iron absorption pathway is unclear. We aimed to elucidate the relationship between the intestinal iron transporter system and Cd-induced iron deficiency anemia. C57BL/6J female and male mice, 129/Sv female mice, and DBA/2 female mice were given a single oral dose of CdCl2 by gavage. After 3 or 24 h, Cd decreased serum iron concentrations and inhibited the expression of iron transport-related genes in the duodenum. In particular, Cd decreased the levels of divalent metal transporter 1 and ferroportin 1 in the duodenum. In addition, human colon carcinoma Caco-2 cells were treated with CdCl2. After 72 h, Cd decreased the expression of iron transport-related factors in Caco-2 cells with a pattern similar to that seen in the murine duodenum. These findings suggest that Cd inhibits iron absorption through direct suppression of iron transport in duodenal enterocytes and contributes to abnormal iron metabolism.

• Authors: Yasuyuki Fujiwara, Jin-Yong Lee, Hiroki Banno, Shunji Imai, Maki Tokumoto, Tatsuya Hasegawa, Yoshiyuki Seko, Hisamitsu Nagase, Masahiko Satoh
• Journal: Toxicology letters (Toxicol Lett) Vol. 332 Pg. 130-139 (Oct 10 2020) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 32645461 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Cation Transport Proteins
• metal transporting protein 1
• solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
• Cadmium
• Iron
• Cadmium Chloride

Topics

• Anemia, Iron-Deficiency (chemically induced)
• Animals
• Biological Transport, Active (drug effects)
• Caco-2 Cells
• Cadmium (pharmacokinetics, toxicity)
• Cadmium Chloride (toxicity)
• Cation Transport Proteins (metabolism)
• Duodenum (drug effects, metabolism)
• Female
• Humans
• Iron (metabolism)
• Liver (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA