Polysulfide and Hydrogen Sulfide Ameliorate Cisplatin-Induced Nephrotoxicity and Renal Inflammation through Persulfidating STAT3 and IKKβ

摘要: Cisplatin, a widely used chemotherapy for the treatment of various tumors, is clinically limited due to its extensive nephrotoxicity. Inflammatory response in tubular cells driving force cisplatin-induced The plant-derived agents are relieve renal dysfunction preclinical studies. Polysulfide and hydrogen sulfide (H2S) ubiquitously expressed garlic, both them documented as potential preventing treating inflammatory disorders. This study was designed determine whether polysulfide H2S could attenuate cisplatin nephrotoxicity through suppression factors. In proximal cells, we found that sodium tetrasulfide (Na2S4), donor, hydrosulfide (NaHS) GYY4137, two donors, ameliorated cisplatin-caused toxicity massive production cytokines, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2). Mechanistically, anti-inflammatory actions Na2S4 may be mediated by persulfidation signal transducer activator transcription 3 (STAT3) inhibitor kappa B kinase β (IKKβ), followed decreased phosphorylation STAT3 IKKβ. Moreover, nuclear translocation (NF-κB), degradation protein alpha (IκBα) induced cisplatin, were also mitigated H2S. mice, after with cisplatin-associated strikingly ameliorated, evidenced measurement serum blood urea nitrogen (BUN) creatinine levels, morphology, expression Our present work suggests afford protection against nephrotoxicity, possibly via persulfidating IKKβ inhibiting NF-κB-mediated cascade. results might shed light on benefits garlic-derived chemotherapy-induced damage.