Treatment with Alamandine Reduces Established Pulmonary Fibrosis: Preliminary Histological, Functional, and Biochemical Insights

Abstract

Pulmonary fibrosis (PF) is a challenging interstitial lung disease with limited therapeutic options. This study explores the therapeutic effects of alamandine (ALA), a renin-angiotensin system peptide, in reversing established fibrotic progression in an experimental model. Male Wistar rats were divided into four groups (n = 5–6/group): control (CO), ALA-treated (ALA), bleomycin-induced fibrosis (BLM), and bleomycin plus ALA treatment (BA). Fibrosis was induced by intratracheal bleomycin (2.5 mg/kg) on day 0. Subcutaneous ALA treatment (50 µg/kg/day) began on day 10 and continued until day 19. Respiratory mechanics, body weight, Ashcroft score, and lung transforming growth factor-beta (TGF-β) content were evaluated. Plasma RAS peptides were quantified by LC-MS/MS. Bleomycin significantly increased respiratory resistance (CO = 0.104 ± 0.026 vs. BLM = 0.159 ± 0.047 cmH₂O.s/mL in CO, p < 0.008) and Ashcroft score, and reduced body weight gain. ALA treatment from day 10–20 markedly improved body weight gain (p < 0.001), reduced Ashcroft score (BLM = 2.23 ± 0.35 vs. BA = 1.21 ± 0.40, p < 0.0001), and decreased lung TGF-β1 content (BLM = 3.70 ± 1.7 vs. BA = 1.10 ± 0.42 pg/mg protein, p < 0.0015). These results were associated with qualitatively improved respiratory effort, suggesting attenuation of bleomycin-induced fibrogenesis. Despite rapid tissue uptake, late ALA treatment was associated with reduced histological fibrosis, lower TGF-β1 content, and improved selected functional and clinical indicators in rats with established pulmonary fibrosis. These findings suggest a potential therapeutic benefit that warrants further dose- and time-ranging studies.