Cytokine production by heavy metals and its significance
| Project/Area Number |
15590112
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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 |
Environmental pharmacy
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| Research Institution | Tokushima Bunri University |
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Principal Investigator |
HIMENO Seiichiro Tokushima Bunri University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20181117)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Cadmium / Cytokine / Manganese / Hepatotoxicity / Cadmium tolerance / Mouse / 金属化合物 / インターロイキン6 / コバルト |
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| Research Abstract |
Previously, we demonstrated that simultaneous administration of MnCl_2 with CdCl_2 resulted in significant reduction of acute Cd toxicity as determined by plasma GPT activity and testicular hemorrhage without affecting tissue accumulation of Cd. CoCl_2 also showed protective effects against acute Cd toxicity in mice. These findings were reconfirmed in metallothionein (MT) knockout mice, suggesting MT is not involved in Mn or Co protection against Cd toxicity. To explore the mechanism of protection against Cd toxicity, we examined the effects of co-administration of these metals with Cd on cytokine production since inflammatory cytokines are known to be involved in liver injury. We also determined plasma levels of acute phase protein, serum amyloid A (SAA), which is induced by cytokines in the liver when inflammation occurred. Among inflammatory cytokines examined, only IL-6 increased in the plasma after the administration of Mn and Co. The peaks of plasma IL-6 levels were observed at 6 h and 3 h by Mn and Co, respectively. Since MT production is, at least in part, involved in the protection against Cd toxicity by Mn, we focused on the effects of Cc on cytokine production. Cd administration itself also increased plasma levels of IL-6 and SAA. Co-administration of Co dose-dependently reduced the Cd-induced increases in plasma GPT activity and SAA levels. The reduced SAA levels in plasma reflected the reduced mRNA levels of SAA1 in the liver as measured by quantitative RT-PCR. However, co-administration of Co with Cd enhanced IL-6 production both at protein levels and mRNA levels. On the other hand, Cd-induced production of TNF-a was reduced by co-administration of Co. Therefore, it is suggested that Cc reduced the production of TNF-a caused by Cd, and consequently protected against hepatotoxicity and SAA production.
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Report
(3 results)
Research Products
(9 results)
