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The effects of gasotransmitters on bronchopulmonary dysplasia

Hai Lin¹, Xinbao Wang²

¹Department of Traditional Chinese Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China.

European Journal of Pharmacology

|February 5, 2020

Insights

Gasotransmitters like nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) show promise in protecting against bronchopulmonary dysplasia (BPD) in preterm infants. Further clinical trials are needed to confirm their therapeutic potential for BPD lung injury.

Area of Science:

Neonatal Medicine
Pulmonary Medicine
Biochemistry

Background:

Bronchopulmonary dysplasia (BPD) is a significant clinical challenge in preterm infants, often resulting from hyperoxia, mechanical ventilation, and inflammation.
Current therapeutic strategies for BPD lack sufficient efficacy, necessitating the exploration of novel treatment approaches.

Purpose of the Study:

To review the role of endogenous gasotransmitters, including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), in mitigating BPD-associated lung injury.
To evaluate the translational potential of gasotransmitters as therapeutic agents for BPD.

Main Methods:

Review of preclinical studies in BPD rodent models investigating the effects of NO, CO, H2S, and hydrogen.
Analysis of clinical trial data on NO inhalation therapy for BPD.
Exploration of the underlying molecular mechanisms, focusing on the Nrf2/HO-1 pathway.

Main Results:

Nitric oxide (NO) inhalation has shown inconsistent results in clinical trials for BPD and is not generally recommended, except for severe pulmonary hypertension.
Carbon monoxide (CO) and hydrogen sulfide (H2S) demonstrated protective effects against lung injury in preclinical BPD models.
The nuclear factor erythroid-derived 2 (Nrf2)/heme oxygenase-1 (HO-1) axis appears to be a key mediator of the protective effects of gasotransmitters.

Conclusions:

Gasotransmitters represent a promising class of molecules with potential therapeutic benefits for BPD.
While preclinical data are encouraging, further clinical investigations are essential to establish the efficacy and safety of gasotransmitters in treating BPD in preterm infants.

Read full analysis

Abstract:

Bronchopulmonary dysplasia (BPD), which remains a major clinical problem for preterm infants, is caused mainly by hyperoxia, mechanical ventilation and inflammation. Many approaches have been developed with the aim of decreasing the incidence of or alleviating BPD, but effective methods are still lacking. Gasotransmitters, a type of small gas molecule that can be generated endogenously, exert a protective effect against BPD-associated lung injury; nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H₂S) are three such gasotransmitters. The protective effects of NO have been extensively studied in animal models of BPD, but the results of these studies are inconsistent with those of clinical trials. NO inhalation seems to have no effect on BPD, although side effects have been reported. NO inhalation is not recommended for BPD treatment in preterm infants, except those with severe pulmonary hypertension. Both CO and H₂S decreased lung injury in BPD rodent models in preclinical studies. Another small gas molecule, hydrogen, exerts a protective effect against BPD. The nuclear factor erythroid-derived 2 (Nrf2)/heme oxygenase-1 (HO-1) axis seems to play a central role in the protective effect of these gasotransmitters on BPD. Gasotransmitters play important roles in mammals, but further clinical trials are needed to explore their effects on BPD.

Keywords:

Bronchopulmonary dysplasia Carbon monoxide Hydrogen Hydrogen sulfide Nitric oxide

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