2007 Fiscal Year Final Research Report Summary
Involvement of iron metabolism in the toxicity of various kinds of environmental pollutants
| Project/Area Number |
18590569
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Jichi Medical University |
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Principal Investigator |
HORIGUCHI Hyogo Jichi Medical University, Center for Community Medicine, Division of Environmental Medicine, associate professor (90254002)
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| Project Period (FY) |
2006 – 2007
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| Keywords | iron / cadmium / estrogen / anemia / erythropoietin / rat / hepcidin / ferroportin |
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| Research Abstract |
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.
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