Comparative renal toxicity of metallothioneins with different cadmium/zinc ratios in rats.
The comparative renal toxicity of rats after injection of cadmium (Cd) and zinc (Zn)-metallothioneins (MTs) with different Cd/Zn ratios at the same dose of 200 micrograms MT-bound Cd/kg was studied. From determination of the urinary excretion of protein, aspartate aminotransferase (AST) and glucose, which are indices of Cd-induced renal damage, the extent of the renal toxicity of the MTs used here was in the order (1 Cd/0Zn)-MT = (2Cd/1Zn)-MT greater than (1Cd/2Zn)-MT greater than (1Cd/6Zn)-MT. The characterization of Cd, Zn and Cu in the urine after injection of MTs was examined using a Sephadex G-75 column. (1Cd/0Zn)-MT injection showed that Cd was present mainly in lower-molecular-weight fractions, with only small amounts of Cd in the MT fraction. Upon injection of other MTs, Cd was present mainly in the MT fraction and increased with decreasing Cd/Zn ratio. Zn was present mainly in lower-molecular-weight fractions and Cu mainly in the MT fraction, indicating the replacement of MT-bound Zn by Cu. The cumulative urinary excretion of Cd during 12 days after injection of MTs decreased with increasing Cd/Zn ratio. The Cd content of the kidney and liver increased with increasing Cd/Zn ratio. The results of this study indicate that in rats injected with MTs with different Cd/Zn ratios, the renal uptake of Cd increases with increasing Cd/Zn ratio, resulting in more severe renal damage.
Kojima
S
S
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Furukawa
A
A
Kiyozumi
M
M
Shimada
H
H
D000818:Animals; D001219:Aspartate Aminotransferases / Q000652:urine; D002104:Cadmium / Q000633:toxicity* / Q000652:urine; D002850:Chromatography, Gel; D003300:Copper / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006029:Glycosuria / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects*; D008668:Metallothionein / Q000008:administration & dosage / Q000633:toxicity*; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015032:Zinc / Q000633:toxicity* / Q000652:urine
D002104:Cadmium; D003300:Copper; D008668:Metallothionein; D001219:Aspartate Aminotransferases; D015032:Zinc