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 burn 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 burn 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 burn-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 burn-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-α, IL-1β, IL-4, IL-6, IL-10 and IL-12) were significantly lower in the plasma of CSE-/-animals after burn than in the plasma of wild-type controls subjected to burns. In conclusion, CSE deficiency improves organ function and attenuates the inflammatory response in a murine model of burn.
Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, USA.
Akbar
A
Ahmad
Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, USA.
Nadiya
N
Druzhyna
Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, USA; Shriners Hospital for Children, Galveston, TX, USA. Electronic address: szabocsaba@aol.com.
Csaba
C
Szabo
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002056:Burns / Q000150:complications* / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000172:deficiency* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D051379:Mice; D009102:Multiple Organ Failure / Q000378:metabolism*
D015415:Biomarkers; D016207:Cytokines; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
Angiogenesis; Burns; Cysteine; Hydrogen sulfide; Inflammation; Oxidative stress