Cystathionine-gamma-lyase deficient mice are protected against the development of multiorgan failure and exhibit reduced inflammatory response during burn

Considering the role of H2S in critical illness, the aim of this study was to compare the outcome of bum in wild-type mice and in mice deficient in CSE, one of the principal mammalian H2S-generating enzymes. Animals were subjected to scald burn. Outcome variables included indices of organ injury, clinical chemistry parameters and plasma levels of inflammatory mediators. Plasma levels of H2S significantly increased in response to bum in wild -type mice, but remained unchanged in CSE-/- mice. Expression of the three H2S-producing enzymes (CSE, CBS and 3-MST) in the lung and liver, and the capacity of tissue homogenates to produce H2S, however, was not affected by burn. In CSE deficient mice there was a significant amelioration of bum-induced accumulation of myeloperoxidase levels in heart, lung, liver and kidney and significantly lower degree of malon dialdehyde accumulation in the heart, lung and kidney than in wild -type mice. CSE deficient mice, compared to wild-type mice, showed a significant attenuation of the bum-induced elevation in circulating alkaline aminotransferase and blood urea nitrogen and creatinine levels, indicative of protective effects of CSE deficiency against burn-induced hepatic, and renal functional impairment. Multiple burn-induced inflammatory mediators (TNF-alpha, IL-1 beta,IL-4, IL-6, IL-10 and IL-12) were significantly lower in the plasma of CSE-/- animals after bum than in the plasma of wild -type controls subjected to bums. In conclusion, CSE deficiency improves organ function and attenuates the inflammatory response in a murine model of bum. (C) 2017 Elsevier Ltd and ISBI. All rights reserved.