Pentoxifylline and prevention of hyperoxia-induced lung injury in neonatal rats

Introduction: Oxygen exposure plays an important role in the pathogenesis of bronchopulmonary dysplasia (BPD). The phosphodiesterase inhibitor pentoxifylline (PTX) has anti-inflammatory and antifibrotic effects in multiple organs. It was hypothesized that PTX would have a protective effect on hyperoxia-induced lung injury (HILI). Methods: Newborn Sprague-Dawley rats were exposed to 95% oxygen (O ₂) and injected subcutaneously with normal saline (NS) or PTX (75mg/kg) twice a day for 9 d. NS-injected, room air-exposed pups were controls. At days 4 and 9, lung tissue was collected to assess edema, antioxidant enzyme (AOE) activities, and vascular endothelial growth factor (VEGF) expression. At day 9, pulmonary macrophage infiltration, vascularization, and alveolarization were also examined. Results: At day 9, treatment with PTX significantly increased survival from 54% to 88% during hyperoxia. Treatment with PTX significantly decreased lung edema and macrophage infiltration. PTX treatment increased lung AOE activities including those of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Furthermore, PTX treatment also increased the gene expression of VEGF189 and VEGF165, increased VEGF protein expression, and improved pulmonary vascularization. Discussion: These data indicate that the reduced lung edema and inflammation, increased AOE activities, and improved vascularization may be responsible for the improved survival with PTX during hyperoxia. PTX may be a potential therapy in reducing some of the features of BPD in preterm newborns.