Time course of arsenite-induced copper accumulation in rat kidney

Oral administration of inorganic arsenic has been shown to lead to an accum ulation of copper in the kidneys of rats and guinea pigs. However, nothing is known about the characteristics and mechanisms of this organ-specific re nal copper accumulation. Many heavy metals accumulate in the kidney, either after environmental or occupational exposure. An additional accumulation o f any other trace metals, even essential ones, may therefore be critical fo r that organ. This prompted us to follow the course of the renal copper acc umulation. Rats were given daily subcutaneous doses of sodium arsenite for 12 d. Each second day, three rats were killed by exsanguination and the liv er, kidneys, and blood removed and analysed for As, Cu, and other trace ele ments by atomic emission spectrometry. Results indicate that arsenic and co pper accumulate in the kidney cortex synchroneously over time. Arsenic also accumulated in the liver and red blood cells (RBC). Copper levels in the R BC and liver as well as copper excretion into the urine were unaffected. Af ter terminating arsenite administration, there was a slow decline in tissue levels of both arsenic and copper, a phenomenon which was parallel for bot h metals. Because the copper level in the liver was not affected, it is con cluded from this study that renal processes and not hepatic or biliary mech anisms might be responsible for the renal copper accumulation. Furthermore, the strong linear correlation (r = 0.85) between arsenic and copper levels in the kidney during and after arsenite administration suggests a function al relationship between arsenic and copper with respect to their retention in the kidney.