Cisplatin (CDDP) is a widely used anticancer drug, but
acute kidney injury (AKI) is one of the most important dose-limiting factors. Trace
metal elements are present in various concentrations in the body and play an important role in maintaining normal vital functions. However, the relationship between CDDP-induced AKI and trace
metal elements is unknown. In this study, we cultured human renal proximal tubular epithelial cells in the presence of CDDP (0, 12.5, 25, 50 μM) and analyzed the concentration of
trace elements in medium after 24 h. We found that CDDP significantly increased the concentrations of
zinc (Zn) and
manganese (Mn) in medium and significantly decreased them in lysate. Therefore, we examined the effects of CDDP (3 mg/kg, i.p.) administration on serum and urinary Zn and Mn concentrations in rats. The results showed that urinary excretion of Zn and Mn increased in CDDP-treated rats 5 days after administration. Also, 5 days after administration, pyknosis, nuclear loss, loss of the brush border membrane, and DNA fragmentation were observed, and serum
creatinine and blood
urea nitrogen levels were found to be significantly increased. These data suggested that 24-h excretion of Zn and Mn might reflect on CDDP induced nephropathy. Monitoring urinary Zn and Mn excretion may be beneficial in detecting AKI, but further studies are needed for clinical application.