Exogenous Hydrogen Sulfide H2S Protects Alveolar Growth in Experimental O2-Induced Neonatal Lung InjuryReportar como inadecuado




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Background

Bronchopulmonary dysplasia BPD, the chronic lung disease of prematurity, remains a major health problem. BPD is characterized by impaired alveolar development and complicated by pulmonary hypertension PHT. Currently there is no specific treatment for BPD. Hydrogen sulfide H2S, carbon monoxide and nitric oxide NO, belong to a class of endogenously synthesized gaseous molecules referred to as gasotransmitters. While inhaled NO is already used for the treatment of neonatal PHT and currently tested for the prevention of BPD, H2S has until recently been regarded exclusively as a toxic gas. Recent evidence suggests that endogenous H2S exerts beneficial biological effects, including cytoprotection and vasodilatation. We hypothesized that H2S preserves normal alveolar development and prevents PHT in experimental BPD.

Methods

We took advantage of a recently described slow-releasing H2S donor, GYY4137 morpholin-4-ium-4-methoxyphenylmorpholino phosphinodithioate to study its lung protective potential in vitro and in vivo.

Results

In vitro, GYY4137 promoted capillary-like network formation, viability and reduced reactive oxygen species in hyperoxia-exposed human pulmonary artery endothelial cells. GYY4137 also protected mitochondrial function in alveolar epithelial cells. In vivo, GYY4137 preserved and restored normal alveolar growth in rat pups exposed from birth for 2 weeks to hyperoxia. GYY4137 also attenuated PHT as determined by improved pulmonary arterial acceleration time on echo-Doppler, pulmonary artery remodeling and right ventricular hypertrophy. GYY4137 also prevented pulmonary artery smooth muscle cell proliferation.

Conclusions

H2S protects from impaired alveolar growth and PHT in experimental O2-induced lung injury. H2S warrants further investigation as a new therapeutic target for alveolar damage and PHT.



Autor: Arul Vadivel, Rajesh S. Alphonse, Lavinia Ionescu, Desiree S. Machado, Megan O’Reilly, Farah Eaton, Al Haromy, Evangelos D. Mic

Fuente: http://plos.srce.hr/



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