| 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)
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| 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)
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| 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.
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