The susceptibility of spontaneously diabetic mice to cadmium-metallothionein nephrotoxicity.
Cadmium metallothionein (CdMT) was injected subcutaneously into obese hyperglycaemic Umeå ob/ob mice or their lean litter mates (normal mice) at doses of 0, 0.1 and 0.4 mg Cd/kg. Proteinuria and calciuria were induced in both types of mice, but in the ob/ob mice this condition developed at a lower dose of CdMT (0.1 mg Cd/kg) than in the normal mice (0.4 mg Cd/kg). These results show, therefore, that Umeå ob/ob mice are particularly susceptible to CdMT-induced nephrotoxicity. The mechanism underlying this phenomenon needs to be further investigated. After the administration of CdMT, a dose-related increase in glycosuria was observed in both types of mice, in spite of decreased levels of serum insulin and glucose. It is suggested that such glycosuria induced by CdMT could be one of the signs of cadmium nephrotoxicity. The results of the present study thus indicate that metabolic changes like those in diabetes may increase susceptibility to cadmium-induced renal tubular damage.
Jin
T
T
Department of Environmental Medicine, University of Umeå, Sweden.
Nordberg
G F
GF
Sehlin
J
J
Leffler
P
P
Wu
J
J
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002118:Calcium / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D007674:Kidney Diseases / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000493:pharmacokinetics / Q000633:toxicity*; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000150:complications; D010179:Pancreas / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced* / Q000150:complications; D014018:Tissue Distribution
D001786:Blood Glucose; D007328:Insulin; C004203:cadmium-binding protein; D008668:Metallothionein; D002118:Calcium