Protective Smell of Hydrogen Sulfide and Polysulfide in Cisplatin-Induced Nephrotoxicity

Though historically known as a toxic gas, hydrogen sulfide (H(2)S) has displayed a new face as the third endogenous gaseous signaling molecule after nitric oxide (NO) and carbon monoxide (CO). Here in this review, we survey the role and therapeutic potential of H(2)S in cisplatin-induced nephrotoxicity. Specifically, reduction of H(2)S by cystathionine γ-lyase (CSE) downregulation upon cisplatin treatment may contribute to cisplatin-induced renal cell injury, possibly by augmentation of endogenous reactive oxygen species (ROS) production, while H(2)S donation may prevent subsequent renal dysfunction by inhibiting NADPH oxidase activation. Intriguingly, H(2)S slow-releasing compound GYY4137 seems to increase the anticancer activity of cisplatin, at least in several cancer cell lines, and this is probably due to its own anticancer effect. However, the efficacy of H(2)S donors in tumor-bearing animals remains to be tested in terms of renal protection and cancer inhibition after receiving cisplatin. Furthermore, accumulative evidence regarding usage of polysulfide, a novel H(2)S derived molecule, in the therapy of cisplatin-induced nephrotoxicity, was also summarized.