ABSTRACT
Background Bronchopulmonary dysplasia (BPD) is a major problem for extremely preterm infants. Glucocorticoids effectively treat BPD; however, they have many side effects. Compound A (Cpd A) is a nonsteroidal Selective Glucocorticoid Receptor Modulator (SEGRM) that acts as a glucocorticoid receptor ligand without inducing the expression of glucocorticoid-response element-driven genes. Cpd A reportedly has anti-inflammatory properties with fewer side effects than glucocorticoids.
Methods Using a bleomycin (Bleo)-induced BPD model, we evaluated the therapeutic effects of Cpd A. 0-day-old Sprague-Dawley rats were administered Bleo for 10 days and treated with dexamethasone (Dex) or Cpd A from day 0 to 13. We evaluated lung pathology by histology and the mRNA levels of interleukin (IL)-1β, transforming growth factor (TGF)-β1 and chemokines, CXCL1 and CCL2.
Results Bleo-treated mice had lungs with impaired alveolarization. Dex and Cpd A treatments improved the alveolar structure, attenuating the lung injury. Bleo-exposed lungs had increased inflammatory cells recruitment and inflammatory mediator mRNA levels. Cpd A treatment reduced inflammatory cells infiltration and CXCL1, CCL2 and TGF-β1 expression.
Conclusion Cpd A improved lung inflammation and alveolar maturation arrest, and restored histological and biochemical changes in a model of BPD. SEGRMs, including Cpd A, are promising candidates for the therapy of BPD.
Impact Statement
○ What is the key message of your article?
Compound A decreased lung inflammation and improved lung morphometric changes in Bleomycin-exposed lungs.
○ What does it add to the existing literature?
Compound A has anti-inflammatory effects in an experimental model of BPD.
○ What is the impact?
SEGRMs, including Cpd A, may be promising candidates for the therapy of BPD.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Statement of financial support No financial assistance was received in support of the study.
Disclosure statement The authors declare no conflicts of interest associated with this manuscript.