Inhibitory action of nedaplatin on Na⁺, K⁺ -ATPase activity and its action on human renal proximal tubule epithelial cells

Abstract

Nedaplatin (NDP), an anticancer platinum complex, is supposed to have stronger action on malignant tumor and less nephrotoxicity than cisplatin. As details of the nephrotoxicity of NDP are not known, we studied the effect of NDP on pig kidney Na⁺, K⁺-ATPase activity and human renal proximal tubule epithelial cells (HRPTE cells) . The pig kidney Na⁺, K⁺-ATPase activity was inhibited by NDP, and the inhibition depended on the incubation time and the concentration of NDP, and the activity was recovered by sulfides. NDP decreased Na⁺, K⁺-ATPase and acid phosphatase activities of HRPTE cells, and the decrease was partially inhibited by addition of 2-mercaptoethanol (2ME) . HRPTE cell death by apoptosis was observed in the presence of NDP, and it was also partially inhibited by 2ME. These results suggest that the inhibition of enzyme activities by NDP may be related to nephrotoxicity, and that some sulfides can recover the activities and may reduce nephrotoxicity.