Protective effect of sulfur-containing molecules against cisplatin-induced nephrotoxicity

Abstract

Cisplatin is one of the most widely used chemotherapeutic agents in the treatment of various types of tumors. The efficacy is dose-dependent, but at higher doses the risk of nephrotoxicity limits its therapeutic potential. Several sulfur-containing molecules function as a cytoprotectant against cisplatin-induced nephrotoxicity. However, the mechanism of cisplatin toxicity in dividing cells differs from that in non-dividing cells, and it is unclear which state of cells are protected by sulfur-containing molecules. In this study, we examined the effect of sulfur-containing molecules against cisplatin toxicity at pre- and post-confluence of renal cell line LLC-PK1. Cytotoxicity was assessed by MTT assay. Sulfite and thiosulfate attenuated cisplatin toxicity at both pre- and post-confluence. Their oxidation products sulfuric acid and tetrathionic acid had no effect, suggesting the reducing potency of sulfite and thiosulfate provides cytoprotection. Tetrasulfide, which is proposed as a novel therapeutic agent to prevent cisplatin toxicity, did not show as much protection as sulfite or thiosulfate in either the pre- or post-confluence state. In addition, tetrasulfide exacerbated cisplatin toxicity at relatively low concentrations. These results suggest that sulfite and thiosulfate can be used as a therapeutic agent against cisplatin-induced nephrotoxicity.