Em. Bombard et al., Time course of chronic oral cadmium nephrotoxicity in Wistar rats: Excretion of urinary enzymes, DRUG CHEM T, 22(4), 1999, pp. 679-703
Twelve male and female Wistar rats each received cadmium (as CdCl2)) in the
ir diet at concentrations of 0, 10, 50, and 250 ppm for 72 weeks. After 1,
4, 8 13, 18 26, 32, 45 57 and 68 week a total of 8 enzymes from different c
ellular compartments of the nephron were measured. At the end of the study
period, the kidneys were examined histopathologically.
Concentrations up to and including 50 ppm did not induce any adverse effect
. At 250 ppm, growth of male and female animals was markedly retarded. Sign
ificantly increased activities of the cytosolic phosphohexose isomerase wer
e excreted by males and females receiving 250 ppm at all timepoints from we
ek 13. The values of the mitochondrial glutamate dehydrogenase were mostly
elevated from week I to 57, however, due to a wide scatter range, were only
occasionally significantly different from control values. The brush border
enzymes (gamma-glutamyl transferase, alkaline phosphatase and leucine aryl
amidase) were not changed in a relevant manner in female rats, while in 250
ppm males the excreted activity of ALP and LAP from week 1 to week 18 and
that of GGT during the entire study period were significantly lower than th
e control values. Excretion of the lysosomal enzymes aryl sulfatase A; beta
-galactosidase, and beta-N-acetyl-D-glucosaminidase was at no time influenc
ed in a noteworthy manner.
Histopathology after 72 weeks revealed chronic but also acute degenerative
changes in the kidneys of 250 ppm males and females. A comparison of publis
hed data on persons having undergone high cadmium exposure with the results
presented here shows remarkable differences.