Pheniramine maleate attenuates oleic acid-induced acute respiratory distress syndrome in rats

Acute respiratory distress syndrome (ARDS) is a common clinical syndrome of acute lung injury with considerable mortality rate of 26-58%. Oleic acid (OA)-induced lung injury that reproduces the early exudative phase of ARDS is an established experimental model of acute lung injury in animals. In this study, we examined the role of antihistaminic drug pheniramine maleate in reversing the oleic acid-induced acute respiratory distress syndrome compared to methylprednisolone, generally used in the treatment of ARDS. Trachea, jugular vein and carotid artery were cannulated in anesthetized rats. Lethal dose of OA (75 μL) was injected i.v. and respiratory frequency (RF), heart rate (HR) and mean arterial pressure (MAP) were determined. At the end of experiment, the lungs were excised for estimation of pulmonary water content and the histological examination. OA produced typical manifestations of ARDS as indicated by profound increase in RF, injury to alveolar-capillary barrier, flooding of alveolar spaces with fluid, influx of inflammatory cells and lethality within 60 min. Along with these changes there was progressive decrease in HR and MAP. In pheniramine maleate pretreated animals, OA did not produce immediate increase in RF and after 60 min there was progressive decrease. There was no pulmonary edema and the histology revealed nearly normal lung parenchyma, less exudation and infiltration. HR and MAP were maintained till 75 min followed by decrease. Survival time was prolonged and 50 % of the animals survived up to 120 min. In another group pretreated with methylprednisolone, OA failed to produce severe changes in RF up to 90 min. Pulmonary water content was significantly less in this group and the histological features exhibited less lung injury as compared to OA treated group. The HR and MAP were maintained till 75 min followed by decrease. Mean survival time of these animals was significantly greater (105 min) than only OA treated animals. Present observations reveal that both pheniramine maleate and methylprednisolone ameliorated OA-induced ARDS in rats.