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.

Study Design

Experimental prospective animal study.

Setting

Animal laboratory of Tongji Hospital, Tongji University, Shanghai, China.

Subjects and 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.