Cadmium, copper, and zinc excretion and their binding to metallothionein in urine of cadmium‐exposed Rats

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Abstract
The urinary excretion of Cd, Cu, and Zn was measured in rats injected with 0.5 mg/kg Cd, sc, 6 d/wk for up to 25 wk. Gel Chromatographic analyses for these urinary metals were also carried out. The Cd excretion slightly increased at first, followed by a rapid increase with concurrent appearance of proteinuria around 6 wk. During these early weeks, excretion of Cu in the urine showed a more pronounced increase and reached a plateau level (three to four times the control value). Zn excretion showed a sharp increase accompanied by proteinuria, following a slight increase, and reached about 10 times the control value. A linear relation was obtained between Cd and both Cu and Zn in the urine before proteinuria appeared. Metallothionein (MT) in the urine was associated only with Cu before the appearance of proteinuria. Cu‐MT increased with increasing excretion of urinary Cu. Cd‐containing MT first appeared in the urine after an onset of proteinuria, but it was still rich in Cu at first. From 10 wk, urinary MT showed an excess increase and contained much more Cd than Cu. Zn‐MT was not observed in the urine. Most of the urinary Zn was recovered from the lower‐molecular‐weight fractions. The results suggest that MT is directly involved in urinary excretion of Cu in the absence of renal damage and in the excretion of Cd as well as Cu after the appearance of toxicity in Cd‐exposed rats.