Growth hormone releasing peptide-6 (GHRP-6) ameliorates acute lung injury and its subsequent evolvement to interstitial fibrosis.

Abstract

Acute lung injury/acute respiratory distress syndrome is a complex, characterized by acute onset, alveolar damage, and progressive hypoxemia. The subsequent proliferative phase drives to pulmonary fibrosis. Lipopolysaccharide (LPS) and zymosan (ZYM) induced lung injury are commonly used biomodels that recapitulate multiple pathogenic hallmarks. We examined the ability of growth hormone releasing peptide 6 (GHRP-6) to attenuate the pulmonary damages associated with intratracheal instillation of LPS or ZYM combined injection with platelet activating factor (PAF) in mice. For the acute scenario, mice received LPS challenge and 6 h later, assigned to normal saline (Control) or to a single administration of each GHRP-6 dose and evolved for 24 h; or mice received four ZYM tracheal instillations and 6 h after, one PAF injection assigned to normal saline (Control) or to five administrations of each GHRP-6 dose and evolved for 15 days. For the chronic scenario, mice were terminated 28 days after receiving a single LPS instillation and seven subsequent daily administrations of GHRP-6; or mice were terminated 28 days after receiving five GHRP-6 therapeutic interventions after four ZYM tracheal instillations and one PAF injection. The acute scenario, GHRP-6 reduced neutrophilic alveolitis, attenuated lung compliance failure, contributed to improve alveolar-capillary permeability, and reduced interleukin-1 beta serum levels. The chronic scenario, GHRP-6 preserved lung parenchymal integrity accounted for meager collagen accumulation. This is the first assessment on the potential protective of GHRP-6 in model of lung damages. This study therefore paves the way for future research on the potential pneumoprotective effects of GHRP-6.