Though historically known as a toxic gas, hydrogen sulfide (H₂S) 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 H₂S in cisplatin-induced nephrotoxicity. Specifically, reduction of H₂S 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 H₂S donation may prevent subsequent renal dysfunction by inhibiting NADPH oxidase activation. Intriguingly, H₂S 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 H₂S 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 H₂S derived molecule, in the therapy of cisplatin-induced nephrotoxicity, was also summarized.
Keywords: GYY4137; NADPH oxidase; cisplatin-induced nephrotoxicity; cystathionine γ-lyase; hydrogen polysulfide; hydrogen sulfide.