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A clearance study of Cd was carried out in rats that had received an intravenous bolus of CdCl2 or Cd-saturated metallothionein-II (Cd-MT-II) at 0.3 mg Cd/kg body weight. Urinary concentrations of Cd, and those corrected by the urine-plasma inulin ratio, were higher, by 2 or 3 orders of magnitude, for Cd-MT-II than for CdCl2. Fractional clearance of Cd was 0.0006 to 0.0029 for CdCl2, and 0.130 to 0.487 for Cd-MT-II. These findings denoted that the glomerular filtration of Cd was greater in the Cd-MT-II administration than in CdCl2 administration. This difference in the glomerular filtration of Cd gave a clear explanation for the greater nephrotoxic potential of Cd-MT-II. Also, our data revealed that when Cd was administered as Cd-MT-II, the concentration of Cd was 20 to 70 times higher at the end-point of the renal tubules than at its starting-point. This and the histopathological reports so far strongly suggest that the distally located tubules are highly resistant to intraluminal Cd.

biological and pharmaceutical bulletin

Clearance Study for the Estimation of Glomerular Filtration of Cd Following the Intravenous Bolus of CdCl2 and Cd-Saturated Metallothionein-II in Rats.