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

Akbar Ahmad, Nadiya Druzhyna, Csaba Szabo

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalBurns
DOIs
StateAccepted/In press - 2017

Keywords

  • Angiogenesis
  • Burns
  • Cysteine
  • Hydrogen sulfide
  • Inflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Surgery
  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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