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

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Zhang H, Zhi L, Moore PK, Bhatia M

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

Am J Physiol Lung Cell Mol Physiol. 2006 Jun;290(6):L1193-201. Epub 2006 Jan 20.

PubMed ID

16428267 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cysteine	Cystathionine beta-synthase	Protein	Humans	Unknown	Not Available	Details
Cysteine	Cystathionine gamma-lyase	Protein	Humans	Unknown	Not Available	Details