Effects of sub-chronic Cd exposure on levels of copper, selenium, zinc, iron and other essential metals in rat renal cortex

Abstract

Cd (Cd) is a nephrotoxic environmental pollutant that causes generalized proximal tubule dysfunction. Even though the specific mechanisms by which Cd damages the kidney have yet to be fully elucidated, there is evidence to suggest that some of these nephrotoxic effects may result from the ability of Cd to alter the levels and function of metals such as Cu, Se, Zn and Fe within the kidney. In order to further explore this issue, we examined the effects of subchronic Cd exposure on tissue levels of a panel of metals (Ca, Cu, Fe, K, Mg, Na, Se and Zn) in the rat renal cortex. Adult male Sprague-Dawley rats were treated with CdCl2 (0.6 mg Cd/kg body weight in isotonic saline by subcutaneous injection, 5 days per week for 6, 9 or 12 weeks). At each time point, 24 h urine samples were collected and assayed for levels of protein, creatinine, β2 microglobulin and cystatin C. Samples of renal cortex were removed and assayed for levels of the metals of interest by inductively-coupled mass spectrometry at Michigan State University. Results showed that at 9 and 12 weeks, Cd caused significant increases in urine volume and urinary protein with no change in creatinine excretion. Increases in the excretion of the urinary biomarkers β2 microglobulin and cystatin C were evident after 6 weeks of Cd exposure. Results of the metal analyses showed that Cd caused significant increases in tissue levels of Cu and Se at all of the time points examined. Tissue levels of Zn were transiently elevated at 6 weeks but declined to control levels at 9 and 12 weeks. Cd caused a significant decrease in levels of Fe at 9 and 12 weeks. Cd had no effects on any of the other metals. Tissue levels of Cd were 530 ± 52, 863 ± 23, 837 ± 23 ppm dry weight at 6, 9 and 12 weeks, respectively. These results indicate that the early stages of Cd nephrotoxicity are associated with alterations in renal tissue levels of Cu, Se, Zn and Fe. The fact that the changes in levels of the metals occurred during the early stages of Cd toxicity raises the possibility that the alterations in renal cortical metal content may play some role in the pathophysiology or Cd-induced injury. Keywords: Kidney, Cadmium, Copper, Selenium, Zinc, Iron