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1998 Fiscal Year Final Research Report Summary

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
Keywordscadmium / renal dysfunction / critical concentration / metallothionein / hepatic function modifier / prevention / 治療
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.

  • Research Products

    (11 results)

All Other

All Publications (11 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2001-10-23  

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