Involvement of the essential metal transporter Zip14 in hepatic Cd accumulation during inflammation

• Published in: Toxicology letters Vol. 218; no. 1; pp. 91 - 96
• Main Authors: Min, Kyong-Son, Takano, Masaoki, Amako, Katsumi, Ueda, Hidenori, Tanaka, Keiichi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 27.03.2013
• Subjects: Acute-Phase Reaction - immunology; Acute-Phase Reaction - metabolism; Animals; Cadmium - metabolism; Cadmium accumulation; Cadmium Chloride - administration & dosage; Cadmium Chloride - pharmacokinetics; Cation Transport Proteins - genetics; Cation Transport Proteins - metabolism; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - metabolism; Deficiency Diseases - complications; Deficiency Diseases - metabolism; Diet; Escherichia coli Infections - immunology; Escherichia coli Infections - metabolism; Essential metals: Inflammation: Interleukin 6; Gene Expression - drug effects; Hexanes - toxicity; Host-Pathogen Interactions; Injections, Intraperitoneal; Interleukin-6 - blood; Iron - deficiency; Iron - metabolism; Lipopolysaccharides - immunology; Liver - chemistry; Liver - drug effects; Liver - metabolism; Male; Mice; Mice, Inbred Strains; RNA, Messenger - metabolism; Turpentine - toxicity; Zinc - deficiency; Zinc - metabolism; Zip 14; Essential metals: Inflammation: Interleukin 6; FPN1; Zip 14; RT-PCR; Cadmium accumulation
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2013.01.010

► Inflammation caused hepatic Cd, Zn, and Fe accumulation. ► Inflammatory IL-6 increased hepatic Zip14 expression. ► Inflammation caused additional hepatic Cd accumulation in Zn-deficient mice. ► Inflammation did not cause hepatic Cd accumulation in Fe-deficient mice. ► Infection did not increase hepatic Cd accumulation or Zip14 expression. Upregulation of Zip14 contributes to hepatic zinc (Zn) and non-transferrin-bound iron (Fe) uptake during infection and inflammation. We investigated whether this essential metal transporter is also involved in hepatic cadmium (Cd) uptake under these conditions. An injection of lipopolysaccharide (LPS), turpentine oil (Tur) and n-hexane (Hex) resulted in an decrease in plasma Zn and Fe concentrations to 25–50% and an increase in hepatic concentrations of both metals to 150–200% of control mice. LPS significantly increased plasma interleukin (IL)-6 levels more rapidly than Tur or Hex. Tur or Hex significantly increased hepatic Zip14 mRNA expression and decreased ferroportin 1 mRNA expression following continuous increase of IL-6 level. Hepatic Cd and Zn concentrations increased significantly after repeated injections of Cd in Tur- or Hex-treated mice fed a control diet. Treatment with Tur or Hex additionally increased hepatic Cd accumulation in Zn-deficient mice, unlike in Fe-deficient mice. These results suggest that Zn transporters, such as Zip14, may be involved in hepatic Cd uptake during inflammation.