Long-Term Exposure to Cadmium Causes Hepatic Iron Deficiency through the Suppression of Iron-Transport-Related Gene Expression in the Proximal Duodenum

Cadmium (Cd) is an environmental pollutant that damages various tissues. Cd may cause a depletion of iron stores and subsequently an iron deficiency state in the liver. However, the molecular mechanism of decreased iron accumulation in the liver induced by long-term exposure to Cd is unknown. In thi...

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Main Authors: Maki Tokumoto, Jin-Yong Lee, Yasuyuki Fujiwara, Masahiko Satoh
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Toxics
Subjects:
Online Access:https://www.mdpi.com/2305-6304/11/7/641
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author Maki Tokumoto
Jin-Yong Lee
Yasuyuki Fujiwara
Masahiko Satoh
author_facet Maki Tokumoto
Jin-Yong Lee
Yasuyuki Fujiwara
Masahiko Satoh
author_sort Maki Tokumoto
collection DOAJ
description Cadmium (Cd) is an environmental pollutant that damages various tissues. Cd may cause a depletion of iron stores and subsequently an iron deficiency state in the liver. However, the molecular mechanism of decreased iron accumulation in the liver induced by long-term exposure to Cd is unknown. In this study, we investigated the hepatic accumulation of iron and the proximal duodenal expression of the genes involved in iron transport using mice chronically exposed to Cd. Five-week-old female C57BL/6J mice were fed a diet containing 300 ppm Cd for 12, 15, 19 and 21 months. The iron concentration in the liver was markedly decreased by Cd. Among iron-transport-related genes in the proximal duodenum, the gene expression of <i>HCP1</i> and <i>Cybrd1</i> was significantly decreased by Cd. <i>HCP1</i> is an influx transporter of heme iron. <i>Cybrd1</i> is a reductase that allows non-heme iron to enter cells. The expression of iron-transport-related genes on the duodenal basolateral membrane side was hardly altered by Cd. These results suggest that long-term exposure to Cd suppresses the expression of <i>HCP1</i> and <i>Cybrd1</i> in the proximal duodenum, resulting in reduced iron absorption and iron accumulation in the liver.
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spelling doaj.art-c85e8b05a3f9413d82bdde3d5fe09fa32023-11-18T21:37:43ZengMDPI AGToxics2305-63042023-07-0111764110.3390/toxics11070641Long-Term Exposure to Cadmium Causes Hepatic Iron Deficiency through the Suppression of Iron-Transport-Related Gene Expression in the Proximal DuodenumMaki Tokumoto0Jin-Yong Lee1Yasuyuki Fujiwara2Masahiko Satoh3Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650, JapanLaboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650, JapanDepartment of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji 192-0392, JapanLaboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650, JapanCadmium (Cd) is an environmental pollutant that damages various tissues. Cd may cause a depletion of iron stores and subsequently an iron deficiency state in the liver. However, the molecular mechanism of decreased iron accumulation in the liver induced by long-term exposure to Cd is unknown. In this study, we investigated the hepatic accumulation of iron and the proximal duodenal expression of the genes involved in iron transport using mice chronically exposed to Cd. Five-week-old female C57BL/6J mice were fed a diet containing 300 ppm Cd for 12, 15, 19 and 21 months. The iron concentration in the liver was markedly decreased by Cd. Among iron-transport-related genes in the proximal duodenum, the gene expression of <i>HCP1</i> and <i>Cybrd1</i> was significantly decreased by Cd. <i>HCP1</i> is an influx transporter of heme iron. <i>Cybrd1</i> is a reductase that allows non-heme iron to enter cells. The expression of iron-transport-related genes on the duodenal basolateral membrane side was hardly altered by Cd. These results suggest that long-term exposure to Cd suppresses the expression of <i>HCP1</i> and <i>Cybrd1</i> in the proximal duodenum, resulting in reduced iron absorption and iron accumulation in the liver.https://www.mdpi.com/2305-6304/11/7/641cadmiumiron deficiencyiron storageiron-transport-related factorproximal duodenum
spellingShingle Maki Tokumoto
Jin-Yong Lee
Yasuyuki Fujiwara
Masahiko Satoh
Long-Term Exposure to Cadmium Causes Hepatic Iron Deficiency through the Suppression of Iron-Transport-Related Gene Expression in the Proximal Duodenum
Toxics
cadmium
iron deficiency
iron storage
iron-transport-related factor
proximal duodenum
title Long-Term Exposure to Cadmium Causes Hepatic Iron Deficiency through the Suppression of Iron-Transport-Related Gene Expression in the Proximal Duodenum
title_full Long-Term Exposure to Cadmium Causes Hepatic Iron Deficiency through the Suppression of Iron-Transport-Related Gene Expression in the Proximal Duodenum
title_fullStr Long-Term Exposure to Cadmium Causes Hepatic Iron Deficiency through the Suppression of Iron-Transport-Related Gene Expression in the Proximal Duodenum
title_full_unstemmed Long-Term Exposure to Cadmium Causes Hepatic Iron Deficiency through the Suppression of Iron-Transport-Related Gene Expression in the Proximal Duodenum
title_short Long-Term Exposure to Cadmium Causes Hepatic Iron Deficiency through the Suppression of Iron-Transport-Related Gene Expression in the Proximal Duodenum
title_sort long term exposure to cadmium causes hepatic iron deficiency through the suppression of iron transport related gene expression in the proximal duodenum
topic cadmium
iron deficiency
iron storage
iron-transport-related factor
proximal duodenum
url https://www.mdpi.com/2305-6304/11/7/641
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