title: Impact of carbon monoxide/heme oxygenase on hydrogen sulfide/cystathionine-γ-lyase pathway in the pathogenesis of allergic rhinitis in guinea pigs.
abstract: OBJECTIVE
  The discovery of carbon monoxide (CO) and hydrogen sulfide (H2S) as pathogenic signaling molecules in airway-related diseases has led to significant insights into the pathophysiologic mechanisms underlying the development of allergic rhinitis (AR). The potential crosstalk between CO and H2S signaling pathways in AR has not been adequately investigated. This study was performed to elucidate the mechanistic relationship between CO and H2S in AR.
  
  
  METHODS
  Experimental prospective animal study.
  
  
  METHODS
  Animal laboratory of Tongji Hospital, Tongji University, Shanghai, China.
  
  
  METHODS
  A well-established model of AR was used whereby guinea pigs (N=24) were randomly divided into 4 treatment groups (n=6 for each group): The first group received ovalbumin only; the second group was administered exogenous hemin, a CO-binding metalloporphyrin; the third group received zinc protoporphyrin, an inhibitor of heme oxygenase-1. A control group was challenged using only saline. Symptoms of AR were recorded, and quantitation of plasma CO and H2S levels was performed. Expression of heme oxygenase-1 and H2S-generating enzyme cystathionine-γ-lyase (CSE) were measured from nasal mucosa.
  
  
  RESULTS
  Plasma CO and heme oxygenase-1 expression levels of nasal mucosa were significantly increased in the AR group compared to controls, whereas H2S concentrations were significantly decreased. Exogenous administration of CO exacerbated allergic symptoms, resulting in higher levels of both CO and heme oxygenase-1 expression, and a further reduction in H2S levels and CSE expression. Zinc protoporphyrin decreased CO concentrations and increased levels of both H2S and CSE expression.
  
  
  CONCLUSIONS
  Results indicated an inverse relationship between H2S levels and CO in the pathogenesis of AR.
authors.affiliation: Department of Otolaryngology, Tongji Hospital, Tongji University, Shanghai, China yu_shaoqing@163.com.
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology, Xuzhou 97th Hospital of PLA, Jiangshu, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Otolaryngology, Tongji Hospital, Tongji University, Shanghai, China.
authors.forename: Na
authors.initials: N
authors.lastname: Che
authors.affiliation: Department of Otolaryngology, Tongji Hospital, Tongji University, Shanghai, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology, Tongji Hospital, Tongji University, Shanghai, China.
authors.forename: Rongming
authors.initials: R
authors.lastname: Ge
mesh_terms: D000393:Air Pollutants / Q000493:pharmacokinetics; D000818:Animals; D000963:Antimetabolites / Q000493:pharmacokinetics; D015153:Blotting, Western; D002248:Carbon Monoxide / Q000493:pharmacokinetics*; D003542:Cystathionine gamma-Lyase / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D006168:Guinea Pigs; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics*; D006862:Hydrogen Sulfide / Q000493:pharmacokinetics*; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism; D011446:Prospective Studies; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D065631:Rhinitis, Allergic / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000393:Air Pollutants; D000963:Antimetabolites; D012313:RNA; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
keywords: allergic; carbon monoxide; cystathionine-β-synthase; cystathionine-γ-lyase; heme oxygenase-1; hydrogen sulfide; rhinitis