OBJECTIVE: To investigate the interaction and involvement of hydrogen sulfide and transient receptor potential vanilloid type 1 in the pathogenesis of sepsis. Hydrogen sulfide has been demonstrated to be involved in many inflammatory states including sepsis. Its contribution in neurogenic inflammation has been suggested in normal airways and urinary bladder. However, whether endogenous hydrogen sulfide would induce transient receptor potential vanilloid type 1-mediated neurogenic inflammation in sepsis remains unknown. DESIGN: Prospective, experimental study. SETTING: Research laboratory. SUBJECT: Male Swiss mice. INTERVENTIONS: Mice were subjected to cecal ligation and puncture-induced sepsis and treated with transient receptor potential vanilloid type 1 antagonist capsazepine (15 mg/kg subcutaneous) 30 mins before cecal ligation and puncture. To investigate hydrogen sulfide-mediated neurogenic inflammation in sepsis, DL-propargylglycine (50 mg/kg intraperitoneal), an inhibitor of hydrogen sulfide formation was administrated 1 hr before or 1 hr after the induction of sepsis, whereas sodium hydrosulfide (10 mg/kg intraperitoneal), a hydrogen sulfide donor, was given at the same time as cecal ligation and puncture. Lung and liver myeloperoxidase activities, liver cystathionine-gamma-lyase activity, plasma hydrogen sulfide level, histopathological examination, and survival studies were determined after induction of sepsis. MEASUREMENTS AND MAIN RESULTS: Capsazepine treatment attenuates significantly systemic inflammation and multiple organ damage caused by sepsis, and protects against sepsis-induced mortality. Similarly, administration of sodium hydrosulfide exacerbates but capsazepine reverses these deleterious effects. In the presence of DL-propargylglycine, capsazepine causes no significant changes to the attenuation of sepsis-associated systemic inflammation, multiple organ damage, and mortality. In addition, capsazepine has no effect on endogenous generation of hydrogen sulfide, suggesting that hydrogen sulfide is located upstream of transient receptor potential vanilloid type 1 activation, and may play a critical role in regulating the production and release of sensory neuropeptides in sepsis. CONCLUSIONS: The present study shows that hydrogen sulfide induces systemic inflammation and multiple organ damage characteristic of sepsis via transient receptor potential vanilloid type 1-mediated neurogenic inflammation.
OBJECTIVE: To investigate the interaction and involvement of hydrogen sulfide and transient receptor potential vanilloid type 1 in the pathogenesis of sepsis. Hydrogen sulfide has been demonstrated to be involved in many inflammatory states including sepsis. Its contribution in neurogenic inflammation has been suggested in normal airways and urinary bladder. However, whether endogenous hydrogen sulfide would induce transient receptor potential vanilloid type 1-mediated neurogenic inflammation in sepsis remains unknown. DESIGN: Prospective, experimental study. SETTING: Research laboratory. SUBJECT: Male Swiss mice. INTERVENTIONS:Mice were subjected to cecal ligation and puncture-induced sepsis and treated with transient receptor potential vanilloid type 1 antagonist capsazepine (15 mg/kg subcutaneous) 30 mins before cecal ligation and puncture. To investigate hydrogen sulfide-mediated neurogenic inflammation in sepsis, DL-propargylglycine (50 mg/kg intraperitoneal), an inhibitor of hydrogen sulfide formation was administrated 1 hr before or 1 hr after the induction of sepsis, whereas sodium hydrosulfide (10 mg/kg intraperitoneal), a hydrogen sulfidedonor, was given at the same time as cecal ligation and puncture. Lung and liver myeloperoxidase activities, liver cystathionine-gamma-lyase activity, plasma hydrogen sulfide level, histopathological examination, and survival studies were determined after induction of sepsis. MEASUREMENTS AND MAIN RESULTS:Capsazepine treatment attenuates significantly systemic inflammation and multiple organ damage caused by sepsis, and protects against sepsis-induced mortality. Similarly, administration of sodium hydrosulfide exacerbates but capsazepine reverses these deleterious effects. In the presence of DL-propargylglycine, capsazepine causes no significant changes to the attenuation of sepsis-associated systemic inflammation, multiple organ damage, and mortality. In addition, capsazepine has no effect on endogenous generation of hydrogen sulfide, suggesting that hydrogen sulfide is located upstream of transient receptor potential vanilloid type 1 activation, and may play a critical role in regulating the production and release of sensory neuropeptides in sepsis. CONCLUSIONS: The present study shows that hydrogen sulfide induces systemic inflammation and multiple organ damage characteristic of sepsis via transient receptor potential vanilloid type 1-mediated neurogenic inflammation.
Authors: Oscar McCook; Peter Radermacher; Chiara Volani; Pierre Asfar; Anita Ignatius; Julia Kemmler; Peter Möller; Csaba Szabó; Matthew Whiteman; Mark E Wood; Rui Wang; Michael Georgieff; Ulrich Wachter Journal: Nitric Oxide Date: 2014-03-18 Impact factor: 4.427
Authors: Karen C Thomas; Jessica K Roberts; Cassandra E Deering-Rice; Erin G Romero; Randal O Dull; Jeewoo Lee; Garold S Yost; Christopher A Reilly Journal: Am J Physiol Lung Cell Mol Physiol Date: 2011-09-23 Impact factor: 5.464
Authors: Samuel P Wanner; Andras Garami; Eszter Pakai; Daniela L Oliveira; Narender R Gavva; Cândido C Coimbra; Andrej A Romanovsky Journal: Cell Cycle Date: 2012-01-15 Impact factor: 4.534