Role of hydrogen sulfide in cecal ligation and puncture-induced sepsis in the mouse.

Abstract

Endogenous hydrogen sulfide (H(2)S) is naturally synthesized in various types of mammalian cells from l-cysteine in a reaction catalyzed by two enzymes, cystathionine-gamma-lyase (CSE) and/or cystathionine-beta-synthase. The latest studies have implied that H(2)S functions as a vasodilator and neurotransmitter. However, so far there is little information about the role played by H(2)S in systemic inflammation such as sepsis. Thus the aim of this study was to investigate the potential role of endogenous H(2)S in cecal ligation and puncture (CLP)-induced sepsis. Male Swiss mice were subjected to CLP-induced sepsis and treated with saline (ip), dl-propargylglycine (PAG, 50 mg/kg ip), a CSE inhibitor, or sodium hydrosulfide (NaHS; 10 mg/kg ip). PAG was administered either 1 h before or 1 h after the induction of sepsis, whereas NaHS was given at the same time of CLP. CLP-induced sepsis significantly increased the plasma H(2)S level and the liver H(2)S synthesis 8 h after CLP compared with sham operation. Induction of sepsis also resulted in a significant upregulation of CSE mRNA in liver. On the other hand, prophylactic as well as therapeutic administration of PAG significantly reduced sepsis-associated systemic inflammation, as evidenced by myeloperoxidase activity and histological changes in lung and liver, and attenuated the mortality of CLP-induced sepsis. Injection of NaHS significantly aggravated sepsis-associated systemic inflammation. Therefore, the effect of inhibition of H(2)S formation and administration of NaHS suggests that H(2)S plays a proinflammatory role in regulating the severity of sepsis and associated organ injury.

• Authors: Huili Zhang, Liang Zhi, Philip K Moore, Madhav Bhatia
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 290 Issue 6 Pg. L1193-201 (Jun 2006) ISSN: 1040-0605 [Print] United States
• PMID: 16428267 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkynes
• Enzyme Inhibitors
• propargylglycine
• Glycine
• Hydrogen Sulfide

Topics

• Alkynes (pharmacology)
• Animals
• Cecum (physiology)
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Glycine (analogs & derivatives, pharmacology)
• Hydrogen Sulfide (blood, pharmacology)
• Liver (drug effects, microbiology, pathology)
• Lung (microbiology, pathology)
• Mice
• Punctures
• Sepsis (etiology, physiopathology)