Exogenous hydrogen sulfide attenuates hyperoxia effects on neonatal mouse airways
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Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice
Published on: October 19, 2013
Colleen M Bartman1, Marta Schiliro1,2, Lisa Nesbitt3
1Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States.
Insights
Supplemental oxygen can harm premature infants
Area of Science:
- Neonatal Medicine
- Pulmonology
- Biochemistry
Background:
- Premature infants (<34 wk gestation) often require supplemental oxygen, increasing risk for chronic airway diseases like pediatric asthma.
- Moderate hyperoxia ( <60% O2) can impair airway smooth muscle function, leading to inflammation, hyperresponsiveness, remodeling, and airflow obstruction.
- Immature antioxidant systems in premature infants heighten susceptibility to oxygen-induced oxidative stress, exacerbating lung injury.
Purpose of the Study:
- To investigate the protective effects of hydrogen sulfide (H2S) against hyperoxia-induced airway damage in neonatal mice.
- To determine if exogenous H2S can mitigate O2-induced changes in airway contractility, thickness, and remodeling.
- To explore potential sex-specific differences in the response to O2 and H2S treatment.
Main Methods:
- Neonatal mice were exposed to moderate hyperoxia (e.g., <60% O2) or normoxia.
- H2S donors were administered to assess their protective effects.
- Functional assessments included lung function tests (flexiVent) and precision-cut lung slices (PCLS) analysis.
- Structural assessments involved histology and immunofluorescence staining.
Main Results:
- Exogenous H2S administration attenuated the detrimental effects of hyperoxia on developing mouse airway structure and function.
- H2S treatment mitigated O2-induced airway hyperreactivity, contractility, airway smooth muscle thickness, and extracellular matrix deposition.
- A sex-specific difference was observed in the response to moderate O2 and H2S treatment in developing mouse airways.
Conclusions:
- Exogenous hydrogen sulfide shows potential as a therapeutic agent to alleviate hyperoxia-induced lung injury in premature infants.
- Low-dose H2S may offer a protective strategy against chronic airway diseases developing in preterm infants.
- The findings highlight the importance of considering sex as a biological variable in hyperoxia-related lung research and treatment.
Abstract:
Supplemental O2 remains a necessary intervention for many premature infants (<34 wk gestation). Even moderate hyperoxia (<60% O2) poses a risk for subsequent airway disease, thereby predisposing premature infants to pediatric asthma involving chronic inflammation, airway hyperresponsiveness (AHR), airway remodeling, and airflow obstruction. Moderate hyperoxia promotes AHR via effects on airway smooth muscle (ASM), a cell type that also contributes to impaired bronchodilation and remodeling (proliferation, altered extracellular matrix). Understanding mechanisms by which O2 initiates long-term airway changes in prematurity is critical for therapeutic advancements for wheezing disorders and asthma in babies and children. Immature or dysfunctional antioxidant systems in the underdeveloped lungs of premature infants thereby heightens susceptibility to oxidative stress from O2. The novel gasotransmitter hydrogen sulfide (H2S) is involved in antioxidant defense and has vasodilatory effects with oxidative stress. We previously showed that exogenous H2S exhibits bronchodilatory effects in human developing airway in the context of hyperoxia exposure. Here, we proposed that exogenous H2S would attenuate effects of O2 on airway contractility, thickness, and remodeling in mice exposed to hyperoxia during the neonatal period. Using functional [flexiVent; precision-cut lung slices (PCLS)] and structural (histology; immunofluorescence) analyses, we show that H2S donors mitigate the effects of O2 on developing airway structure and function, with moderate O2 and H2S effects on developing mouse airways showing a sex difference. Our study demonstrates the potential applicability of low-dose H2S toward alleviating the detrimental effects of hyperoxia on the premature lung.NEW & NOTEWORTHY Chronic airway disease is a short- and long-term consequence of premature birth. Understanding effects of O2 exposure during the perinatal period is key to identify targetable mechanisms that initiate and sustain adverse airway changes. Our findings show a beneficial effect of exogenous H2S on developing mouse airway structure and function with notable sex differences. H2S donors alleviate effects of O2 on airway hyperreactivity, contractility, airway smooth muscle thickness, and extracellular matrix deposition.
