Protection against cadmium-metallothionein nephrotoxicity in streptozotocin-induced diabetic rats: role of increased metallothionein synthesis induced by streptozotocin

Toxicology. 1996 Jan 8;106(1-3):55-63. doi: 10.1016/0300-483x(95)03164-b.

Abstract

Protection against the development of nephrotoxicity following the administration of cadmium-metallothionein (CdMT) at a dose of 0.4 mg Cd per kg body weights was studied in streptozotocin (STZ)-induced diabetic rats. Six groups of Wistar male rats were used (Groups A and B, Groups A1 and C, and Groups A2 and D were injected intraperitoneally with STZ at doses of 0, 50 and 100 mg/kg, respectively, and then 6 days later, Groups B, C and D were injected subcutaneously with CdMT). Proteinuria, albuminuria and transferrinuria were observed after the administration of CdMT, and a dose-related decrease following the increased STZ dose was seen in Groups B, C and D. The concentrations of metallothionein (MT) and zinc (Zn) in liver and kidney were dose-dependently increased in Groups B, C and D. Induction of increased MT synthesis in liver and kidney as the result of the STZ treatment was observed in this study. In particular, a remarkable increase in liver MT concentration was induced by STZ, and transport to the kidney of MT synthesized in liver may perhaps explain the protection against cadmium nephrotoxicity in STZ-induced diabetic rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadmium / toxicity*
  • Chromatography, Gel
  • Cytosol / metabolism
  • Diabetes Mellitus, Experimental / metabolism*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / prevention & control
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Metallothionein / biosynthesis*
  • Metallothionein / toxicity*
  • Metallothionein / urine
  • Metals / urine
  • Proteinuria / chemically induced
  • Rats
  • Rats, Wistar
  • Streptozocin / pharmacology*
  • Transferrin / urine
  • Urination / drug effects

Substances

  • Metals
  • Transferrin
  • cadmium-binding protein
  • Cadmium
  • Streptozocin
  • Metallothionein