Fujiwara Yasuyuki, Lee Jin-Yong, Banno Hiroki, Imai Shunji, Tokumoto Maki, Hasegawa Tatsuya, Seko Yoshiyuki, Nagase Hisamitsu, Satoh Masahiko
Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, Nagoya, 464-8650, Japan; Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, 192-0392, Japan.
Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, Nagoya, 464-8650, Japan.
Toxicol Lett. 2020 Oct 10;332:130-139. doi: 10.1016/j.toxlet.2020.07.005. Epub 2020 Jul 6.
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 CdCl 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 CdCl. 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.
镉(Cd)是一种环境污染物,可在肾脏、肝脏和肺等多种组织中引发毒性作用。镉还可导致铁代谢异常,进而引发贫血。铁稳态受肠道吸收调节。然而,镉是否影响铁吸收途径尚不清楚。我们旨在阐明肠道铁转运系统与镉诱导的缺铁性贫血之间的关系。通过灌胃给C57BL/6J雌雄小鼠、129/Sv雌性小鼠和DBA/2雌性小鼠单次口服氯化镉。3或24小时后,镉降低了血清铁浓度,并抑制了十二指肠中铁转运相关基因的表达。特别是,镉降低了十二指肠中二价金属转运体1和铁转运蛋白1的水平。此外,用氯化镉处理人结肠癌Caco-2细胞。72小时后,镉降低了Caco-2细胞中铁转运相关因子的表达,其模式与在小鼠十二指肠中观察到的相似。这些发现表明,镉通过直接抑制十二指肠肠细胞中的铁转运来抑制铁吸收,并导致铁代谢异常。