Influence of different degrees of reduced renal mass on the renal and hepatic disposition of administered cadmium.
The present study was designed to evaluate, in rats, the effect of varying degrees of reduced renal mass on the disposition of administered cadmium. As part of this evaluation, the intrarenal, hepatic, and hematological disposition of cadmium and the urinary and fecal excretion of cadmium were studied and characterized in control, uninephrectomized (NPX), and 75% nephrectomized (75% NPX) rats 1 d, 2 d, and 7 d after the intravenous injection of a nonnephrotoxic 8.9 mumol/kg dose of cadmium chloride. Renal accumulation of cadmium, especially in the cortex and outer stripe of the outer medulla, was reduced significantly in the 75% NPX rats, but not in the NPX rats, between d 2 and 7 after the injection of cadmium. The diminution in the renal accumulation of cadmium in the 75% NPX rats was most likely due to diminished glomerular filtration rate and renal clearance of cadmium induced by 75% nephrectomy. Despite reduced glomerular filtration rate, the cumulative urinary excretion of cadmium in the 75% NPX rats was significantly greater than that in either the NPX rats or the control rats. It should be mentioned, however, that very little of the administered dose of cadmium was excreted in the urine by any of the three groups of rats. Interestingly, the content of cadmium in the liver was significantly greater in 75% NPX rats than in NPX or control rats between d 1 and 7 after the injection of cadmium. Moreover, the 75% NPX rats excreted significantly less cadmium in the feces over the 7 d of study than did the other 2 groups of rats, indicating that 75% nephrectomy causes a significant alteration in one or more of the mechanisms involved in the fecal excretion of cadmium. In summary, the findings from the present study indicate that the renal and hepatic handling of administered cadmium in rats changes significantly when renal mass is reduced by 75%. Further studies are needed to better characterize the effects of reductions of renal mass, which impair renal function significantly, on both the disposition and toxicity of cadmium in renal and hepatic tissues.
Zalups
R K
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Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia, USA.
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002104:Cadmium / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D005243:Feces / Q000737:chemistry; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy / Q000009:adverse effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D002104:Cadmium; D019256:Cadmium Chloride