Involvement of iron metabolism in the toxicity of various kinds of environmental pollutants

以非缺铁或缺铁饲料喂养的大鼠，腹腔注射镉（2 mg/kg）。C.每周2次，持续1-3个月，以研究铁代谢改变以及铁缺乏和溶血性贫血在通过促红细胞生成素（Epo）产生减少的镉诱导的肾性贫血中的参与。注射镉后1个月，大鼠无肾损伤，并显示肾性贫血，由功能性Epo抑制引起。另一方面，在3个月时，大鼠除了缺铁和溶血性贫血之外，还由于肾Ero产生细胞的破坏而患有肾性贫血，表现出严重的贫血。从外周血和尿、组织学和器官铁浓度、铁动力学和铁代谢相关基因表达分析等方面证实了其作用机制。首先，镉诱导红细胞溶血，随后释放铁并在器官中积累。同时，缺Epo导致的铁利用率降低，促进了铁在器官中的积累。然而，由于铁的无效利用，血红蛋白合成减少，表现为“明显贫血”。总之，由于缺铁、溶血性贫血和肾性贫血的共同作用，慢性镉中毒大鼠贫血进展迅速。C.雌激素（E_2）（10、100、1000 μ g/kg）每周3次，连续2个月，观察E_2对铁代谢的影响。正常情况下，E_2呈剂量依赖性地抑制肠铁吸收和各器官铁摄取，其机制可能是由于肝铁调素诱导增加，十二指肠促铁转运蛋白减少所致。E_2可促进缺铁大鼠小肠铁吸收和各器官铁摄取，其机制可能与十二指肠膜铁转运蛋白、DMT-1、cybrd 1和hephaestin表达增加有关。

Rats that were fed with non-iron deficiency or iron deficiency diet were injected with cadmium (Cd) (2mg/kg) s. c. twice a week for 1-3 months in order to investigate the involvement of changed iron metabolism as well as iron deficiency and hemolytic anemia in Cd-induced renal anemia through hypoproduction of erythmpoietin (Epo). At 1 month after Cd injection, the rats had no renal injury and showed renal anemia resulted from functional Epo suppression. On the other hand, at 3 months, the rats suffered from renal anemia due to the destruction of renal Epo-producing cells in addition to iron deficiency and hemolytic anemia, showing severe anemia. The mechanism was demonstrated as below from the examinations of peripheral blood and urine, histology and iron concentration in organs, iron kinetics, and analyses of iron metabolism-related gene expression. First of all, Cd induces hemolysis on erythrocytes, followed by iron release and the resultant accumulation in organs. At the same time, the decreased iron utilization derived from Epo deficiency enhances iron accumulation in organs. However, hemoglobin synthesis is decreased because of the ineffective iron utilization, showing “apparent anemia". In short, anemia would progress rapidly in chronic Cd intoxication due to the mutual effects of iron deficiency, hemolytic and renal anemia.Rats were injected s. c. with estrogen (E_2) (10, 100, 1000 ug/kg) three times a week for 2 months to observe the effects of E_2 on iron metabolism. E_2 suppressed iron absorption from intestines and iron uptake into organs dose-dependently in a normal condition, which would be derived from the decrease of duodenal frroportin following the increase of hepatic hepcidin induction. On the other hand, E_2 increased iron absorption from intestines and iron uptake into organs in iron deficiency, which would be derived from the duodenal increases in ferroportin, DMT-1, cybrd 1 and hephaestin expression.