THE ROLE AND THERAPEUTIC POTENTIAL OF HYDROGEN SULFIDE AND HYDROGEN POLYSULFIDE IN CISPLATIN NEPHROTOXICITY

Abstract

The current research aimed to explore the role and therapeutic potential of hydrogen sulfide (H2S) and hydrogen polysulfide (H2Sn) in cisplatin nephrotoxicity. Our results indicate that cisplatin led to the reduction of endogenous H2S which may contribute to subsequent renal cell death. H2S donors like NaHS and GYY4137 ameliorated cisplatin caused renal toxicity probably through suppressing the activation of NADPH oxdiase. Importantly, GYY4137 not only ameliorated cisplatin caused renal injury but also added on more anti-cancer activity to cisplatin in cancer cell lines. Our results also showed that polysulfide donor Na2S4 ameliorated cisplatin caused renal toxicity probably through suppressing ROS generation. Additionally, polysulfide may inhibit ROS production by lessening NADPH oxidase activation and inducing Nrf2 nucleus translocation simultaneously. Importantly, Na2S4 possessed anti-cancer effect and added on more anti-cancer effect to cisplatin in cancer cell lines. Therefore, H2S and H2Sn may be novel targets for the treatment of cisplatin nephrotoxicity.