Medicinal Chemistry

Protective Effect of ATRA on Bleomycin Induced Lung Fibrosis in Rat

Abstract

Serairi Beji Raja, Msilini Najoua, Abidi Anouar, Saidi Oussama, Jameleddine Saloua and Ksouri Riadh

All-trans-retinoic acid (ATRA), an active metabolite of vitamin A, is known to affect cell differentiation, proliferation, and development. Pulmonary fibrosis is one of the most common chronic interstitial lung diseases with high mortality rate after diagnosis and limited successful treatment. The aim of this study is to assess the effects of ATRA against bleomycin-induced pulmonary fibrosis in rats. Animals were intratracheally instillated with bleomycin and/or intraperitoneally administered with ATRA. On day 28, rats were sacrificed and histological changes in the lungs were evaluated. Moreover, malondialdehyde (MDA) content, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in serum and lung, were achieved. Results displayed that rat body weight decreased while fibrosis score and inflammatory index in lung tissue were significantly increased, after bleomycin instillation. Administration of bleomycin followed by ATRA reduced bleomycin–induced weight loss, decreased the lung index and the inflammatory indices. Histopathological examination confirmed the antifibrotic effect of ATRA which apparently attenuated the degree of pulmonary fibrosis. In addition, data showed that ATRA significantly increased SOD, CAT and GPx levels as compared to bleomycin group (G2) concomitant to the decrease of MDA content in lung homogenates. These findings indicate that ATRA treatment significantly attenuated the increased pulmonary damage induced by bleomycin.