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

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.