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

以非缺铁饲料和缺铁饲料喂养的大鼠，每周两次注射镉(Cd)S，连续1~3个月，以探讨铁代谢的改变以及铁缺乏和溶血性贫血在Cd所致肾性贫血中的作用。Cd注射后1个月，大鼠肾脏未见损伤，表现为功能性EPO抑制所致的肾性贫血。3个月时，除缺铁、溶血性贫血外，由于肾脏EPO产生细胞的破坏而出现肾性贫血，表现为严重贫血。从外周血、尿、组织学、脏器铁浓度、铁动力学、铁代谢相关基因表达分析等方面对其作用机制进行了初步探讨。首先，Cd诱导红细胞溶血，然后释放铁并在器官中积累。同时，EPO缺乏导致铁利用率下降，增加了器官中铁的积累。然而，由于铁的有效利用，血红蛋白合成减少，表现为明显的贫血。总之，在慢性镉中毒时，由于缺铁、溶血性和肾性贫血的相互作用，贫血会迅速发展。采用S大鼠，每周三次注射雌激素(E_2)(10,100,1000微克/公斤)，连续2个月，观察E_2对铁代谢的影响。在正常情况下，E_2呈剂量依赖性地抑制肠道铁吸收和器官铁吸收，这可能是由于肝脏海普西丁诱导增加后十二指肠froportin减少所致。另一方面，E_2促进缺铁大鼠肠道铁吸收和器官铁吸收，这可能是由于十二指肠铁蛋白、DMT-1、Cybrd 1和Hephestn表达增加所致。

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.