Modulatory effect of D-pinitol on bleomycin-induced pulmonary fibrosis in rats

Abstract

Objective: To assess the effect of D-pinitol on pulmonary fibrosis induced by bleomycin. Methods: Sprague-Dawley rats received intratracheal bleomycin (6 IU/kg) to induce pulmonary fibrosis, followed by administration of either D-pinitol (5, 10, or 20 mg/kg) or vehicle or methylprednisolone (10 mg/kg) over 28 days after bleomycin administration. Lung function, biochemical parameters, serum biochemistry, mRNA expressions, and histological features were observed. Results: D-pinitol at 10 and 20 mg/kg significantly (P<0.05) attenuated bleomycin-induced bronchoalveolar lavage fluid, decreased myeloperoxidase, nitric oxide, malondialdehyde levels, and increased glutathione and superoxide dismutase level. D-pinitol also improved lung function (enhanced pause, frequency of breathing, expired volume, and tidal volume). Besides, D-pinitol significantly (P<0.05) upregulated Nrf2 and downregulated mRNA expressions of TGF-β, collagen-1, and Smad-3. Furthermore, considerably less inflammation (peribronchial, perivascular, and total), Ashcroft, and interstitial fibrosis scores were observed in the D-pinitol group. Conclusions: D-pinitol exerts its effect against bleomycin-induced pulmonary fibrosis via antioxidative and anti-fibrotic pathways.

Keywords

• antioxidant; bleomycin; collagen-1; d-pinitol; pulmonary fibrosis; smad-3; tgf-β