Hydrogen sulfide protects from acute kidney injury via attenuating inflammation activated by necroptosis in dogs

BACKGROUND: The treatment of acute kidney injury (AKI), a common disease in dogs, is limited. Therefore, an effective method to prevent AKI in veterinary clinics is particularly crucial. OBJECTIVES: Hydrogen sulfide (H(2)S) is the third gaseous signal molecule involved in various physiological functions of the body. The present study investigated the effect of H(2)S on cisplatin-induced AKI and the involved mechanisms in dogs. METHODS: Cisplatin-injected dogs developed AKI symptoms as indicated by renal dysfunction and pathological changes. In the H(2)S-treated group, 50 mM sodium hydrosulfide (NaHS) solution was injected at 1 mg/kg/h for 30 min before cisplatin injection. After 72 h, tissue and blood samples were collected immediately. We performed biochemical tests, optical microscopy studies, analysis with test kits, quantitative reverse-transcription polymerase chain reaction, and western blot analysis. RESULTS: The study results demonstrated that cisplatin injection increased necroptosis and regulated the corresponding protein expression of receptor interacting protein kinase (RIPK) 1, RIPK3, and poly ADP-ribose polymerase 1; furthermore, it activated the expressions of inflammatory factors, including tumor necrosis factor-alpha, nuclear factor kappa B, and interleukin-1β, in canine kidney tissues. Moreover, cisplatin triggered oxidative stress and affected energy metabolism. Conversely, an injection of NaHS solution considerably reduced the aforementioned changes. CONCLUSIONS: In conclusion, H(2)S protects the kidney from cisplatin-induced AKI through the mitigation of necroptosis and inflammation. These findings provide new and valuable clues for the treatment of canine AKI and are of great significance for AKI prevention in veterinary clinics.