Hydrogen sulfide promotes transient receptor potential vanilloid 1-mediated neurogenic inflammation in polymicrobial sepsis.
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.


METHODS
Prospective, experimental study.


METHODS
Research laboratory.


METHODS
Male Swiss mice.


METHODS
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.


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.
Ang
Seah-Fang
SF
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Moochhala
Shabbir M
SM
Bhatia
Madhav
M
D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D009102:Multiple Organ Failure / Q000378:metabolism; D020078:Neurogenic Inflammation / Q000503:physiopathology*; D009195:Peroxidase / Q000378:metabolism; D018805:Sepsis / Q000378:metabolism* / Q000503:physiopathology; D013440:Sulfides / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000187:drug effects* / Q000502:physiology; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology
D000480:Alkynes; D013440:Sulfides; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D050051:Transient Receptor Potential Channels; C009055:propargylglycine; D009195:Peroxidase; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; C071423:capsazepine; D002211:Capsaicin; D005998:Glycine; D006862:Hydrogen Sulfide