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

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.