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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MDPI AG
2023-07-01
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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 |
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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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