The role of hydrogen sulphide in hepatic and renal injury in an experimental model of scald burn in the rat

Patricia Marques1, João Rocha1, Pedro Baracho1, Rui Pinto1, Bruno Sepodes1, Christoph Thiemermann2, Helder Mota-Filipe1
1Unit of Pharmacology and Pharmacotoxicology - Faculty of Pharmacy of the University of Lisbon, Lisbon, Portugal, 2The William Harvey Research Institute, London, UK

Evidence available so far supports a pro-inflammatory role for the gaseous mediator hydrogen sulphide (H2S). The present study aimed to investigate the role of endogenous and exogenous H2S in an experimental model of burn injury. Sixty-seven anesthetized and shaved male Wistar rats (280-450g) were randomly allocated into 6 experimental groups and subjected to a tracheotomy, after which they received a 30% total body surface area third-degree burn by immersion in 99°C water for 10 seconds, with exception of the sham group which was immersed in water at room temperature. Six hours after burn injury, blood samples were collected for determination of biochemical markers of liver injury and kidney dysfunction. Pre-treatment with propargylglycine (PAG, an irreversible inhibitor of cystathionine-γ-lyase (CSE), an enzyme responsible for H2S formation in liver and kidney) significantly reduced the burn-induced hepatic injury (ALT: 27±6 vs. 256±60 IU/L). Treatment with sodium hydrosulphide (NaHS, a donor of H2S) significantly increased hepatic injury (ALT: 690±164 vs. 256±60 IU/L; AST: 1569±331 vs. 631±55 IU/L). In what concerns the kidney function, neither PAG (urea: 110±2 vs. 114±4 mg/dL; creatinine: 2,20±0,14 vs. 1,58±0,16 mg/dL) nor NaHS (urea: 116±5 vs. 114±4 mg/dL; creatinine: 2,30±0,30 vs. 1,58±0,16 mg/dL) were able to improve the burn-induced renal dysfunction. In conclusion, with this study we demonstrate that: i) H2S is involved in the pathogenesis of burn injury and, ii) inhibition of CSE (and subsequently H2S production) seems to protect the liver from burn-induced injury in the rat, while in the kidney the functional role of this gaseous mediator is still not very clear.