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

Department of Pharmacology, National University of Singapore, Singapore

Submitted 18 November 2005 ; accepted in final form 16 January 2006

Endogenous hydrogen sulfide (H₂S) is naturally synthesized in various types of mammalian cells from L-cysteine in a reaction catalyzed by two enzymes, cystathionine--lyase (CSE) and/or cystathionine--synthase. The latest studies have implied that H₂S functions as a vasodilator and neurotransmitter. However, so far there is little information about the role played by H₂S in systemic inflammation such as sepsis. Thus the aim of this study was to investigate the potential role of endogenous H₂S 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 H₂S level and the liver H₂S 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 H₂S formation and administration of NaHS suggests that H₂S plays a proinflammatory role in regulating the severity of sepsis and associated organ injury.

DL-propargylglycine; cystathionine--lyase; myeloperoxidase

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