Anti-Fibrotic Effect of REV-5901 in Bleomycin-Induced Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is a progressive lung disease and has a bad prognosis with median survival ranging from 2.5 to 3.5 years. Leukotrienes which are eicosanoid lipid mediators synthesized from arachidonic acid by 5-lipoxygenase (5-LOX) enzyme have been associated with PF. REV-5901 is potent 5-LOX inhibitor; however, its role in PF has not been studied. We demonstrate that REV-5901 has an inhibitory effect on bleomycin (BLM)-induced PF in both in vitro and in vivo models. REV-5901 reduced expression of BLM induced key fibrotic markers in both cells and animal samples. Histopathological analysis of lung tissue demonstrated an alleviating effect on fibrosis with inhibitor treatment. We also observed downregulation of 5-LOX, pAkt and VEGF expressions upon treatment with inhibitor indicating involvement of both lipid and angiogenic pathways in the regulatory effect of REV-5901. Overall, our data suggests REV-5901 demonstrates an anti-fibrotic effect on BLM-induced PF, which warrants further investigation. [ABSTRACT FROM AUTHOR]