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.
Jin
T
T
Department of Environmental Medicine, University of Umeå, Sweden.
Nordberg
G
G
Sehlin
J
J
Vesterberg
O
O
D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002850:Chromatography, Gel; D003600:Cytosol / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000633:toxicity* / Q000652:urine; D008670:Metals / Q000652:urine; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000494:pharmacology*; D014168:Transferrin / Q000652:urine; D014554:Urination / Q000187:drug effects
D008670:Metals; D014168:Transferrin; C004203:cadmium-binding protein; D002104:Cadmium; D013311:Streptozocin; D008668:Metallothionein