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Plasma cadmium-metallothionein, new and ideal biomarker, based on its mechanism

Research Project

Project/Area Number 09470103
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionJICHI MEDICAL SCHOOL

Principal Investigator

NOMIYAMA Kazuo  Jichi Medical School, Professor, 医学部, 教授 (80048967)

Co-Investigator(Kenkyū-buntansha) SAKURAI Hiroshi  Kyoto Pharmaceutical School, Professor, 薬学部, 教授 (30065916)
YOKOI Katsuhiko  Jichi Medical School, Assistant Professor, 医学部, 講師 (10200883)
NOMIYAMA Hiroko  Jichi Medical School, Assistant Professor, 医学部, 講師 (70049039)
HARADA Akira  Kansai Industrial Health Technical Center, Director, 所長
MASAOKA Toshio  Azabu University, Professor, 医学部, 教授 (30063978)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 1998: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1997: ¥4,500,000 (Direct Cost: ¥4,500,000)
Keywordscadmium / renal dysfunction / critical concentration / metallothionein / hepatic function modifier / prevention / 治療 / メタロチオライン / 肝機能異常 / 腎機能異常 / 回復 / バイオマーカー / メタロチオネイン / アポトーシス / 酸化窒素
Research Abstract

Cadmium has been believed to induce renal dysfunction when cadmium in the renal cortex exceeds 200 μg/g (WHO, 1992). Because the biological half time cadmium in the renal cortex is very long such as 20-30 years, cadmium-induced renal dysfunction has been believed not to recover (WHO, 1992). However, it is true that cadmium-induced renal dysfunction is reversible after termination of cadmium exposure. We then proposed the mechanism of cadmium-induced renal dysfunction as follows : (1) cadmium taken into the body accumulates in the liver in a chemical form of cadmium-metallothionein (CdMT), (2) cadmium induces hepatic dysfunction, (3) CdMT leaked out from the liver into the blood stream, (4) CdMT easily passes through glomeruli because of its smaller molecular size (6,000), (5) and then it is reabsorbed at the renal tubules. (6) CdMT was split into cadmium ion and metallothionein, (7) cadmium ion injures tubular membrane to result in renal dysfunction (Nomiyama and Nomiyama, 1994).
The following results approved our proposed mechanism of cadmium-induced dysfunction : (1) critical concentration of cadmium in the renal cortex varied with exposure level, such as 275, 296 and 222 μgCd/g in rabbits given cadmium at a daily dose of 0.3, 1 and 3 mgCd/kg. On the contrary, (2) the critical concentration of plasma cadmium metallothionein (CdMT) in rabbits given cadmium at a daily dose of 0.3, 1 and 3 mgCd/kg was the same as 60-75μgCd/l. (3) After termination of cadmium exposure, cadmium-induced renal dysfunction was reversed with the decrease in plasma CdMT. In addition, (4) glycyrrhizin, hepatic function modifier, prevented cadmium-induced renal dysfunction.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Nomiyama K, et al: "Cadmium-induced reval dysfunction : New mechanism, and prereution"J. Trace Elem Explt Med. 11. 275-288 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nomiyama K, et al: "Plasma Cadmium-metallothionein ; a biological exposure index for cadmium-induced reval dysfunction"Toxicology. 129. 157-168 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nomiyama K, et al: "Mechanism of improved Cadmium-induced reval dysfunction after cessation of cadmium exposure"Metallothionein IV. 471-472 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nomiyama K et al: "Cadmium-induced renal dysfunction : New mechanism, treatment and prevention"J Trace Elem Exptl Med. 11. 275-288 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nomiyama K et al: "Plasma cadmium-metallothionein, a biological exposure index for cadmium-induced renal dysfunction"Toxicology. 129. 157-168 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nomiyama K et al: "Mechanism of improved cadmium-induced renal dysfunction after cessation of cadmium exposure ( preliminary report )"Metallothionein. IV. 471-472 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nomiyama K et al: "Mechanism of improvement of cadmium-induced renal dysfunction after termination of cadmium exposure"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nomiyama K et al: "Critical concentration of cadmium in rabbit renal cortex varies by the exposure level"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nomiyama K et al: "Glycyrrhizin moderates cadmium-induced renal dysfunction"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nomiyama K et al: "Cadmium-induced renal dysfunction was improved by treating hepatic injury with acetazolamide"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nomiyama K et al: "Glycyrrhizin accelerated recovery from cadmium-induced renal dysfunction"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K Nomiyama et al: "Cadmium-induced renaldysfunction:New mechanism,treatment and preveution" J.Trace Elements Exp Med. 11. 275-288 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Nomiyama et al: "Plasma cadmium-metallothionein,a biological exposure index for codmium-induced dysfunction,based on the mechanism of its action" Toxicology. 129. 157-168 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Nomiyama et al: "Mechanism of improved cadmium-induced revel dysfunction after cessation of cadmium exposure" Metallothionein IV. 471-472 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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