Effect of long-term administration of amiodarone on rat lung and the possible protective role of vitamin E: a histological and immunohistochemical study

Introduction: Amiodarone is gaining support as a first-line antiarrhythmic drug despite its potentially fatal pulmonary complications involving inflammation and fibrosis.Objective: This study was undertaken to investigate the effect of long-term amiodarone administration and withdrawal on the histological structure of rat lung. In addition, the possible protective role of vitamin E supplementation was studied.Materials and methods: This study was carried out on 36 adult male albino rats, which were divided into four groups: group I, which was considered as control; group II (amiodarone-treated group), which received amiodarone orally in a daily dose of 30 mg/kg body weight for 12 weeks; group III (withdrawal group), which received the same dose of amiodarone for 12 weeks and were sacrificed 6 weeks after withdrawal of the drug; and group IV (protected group), which received vitamin E orally in a daily dose of 100 mg/kg body weight simultaneously with amiodarone for 12 weeks. At the time of sacrifice, the lungs were dissected and tissue samples were processed for both light and electron microscopic studies. Immuohistochemical study using anti-CD68 for showing alveolar macrophages was also performed and the number of positively stained cells was morphometrically estimated and statistically analyzed.Results: Administration of amiodarone alone showed an alteration in the lung architecture in the form of collapsed alveoli with evident proliferation and vacuolation of pneumocytes type II. Thickening of interalveolar septa, cellular infiltration, and collagen deposition associated with an increased number of macrophages as proved by the morphometric study were demonstrated. Intrabronchial cellular debris and vascular congestion were also observed. Coadministration of amiodarone with vitamin E showed a considerable degree of preservation of the pulmonary alveolar architecture; however, a mild improvement in the lung injury was observed in animals after amiodarone withdrawal. The alveoli were lined mainly by vacuolated pneumocytes type II with moderately thickened interalveolar septa.Conclusion: From this study it could be concluded that prolonged administration of amiodarone in rats can induce severe lung damage. Withdrawal of the drug showed little improvement of this harmful effect but concomitant administration of vitamin E effectively protected the lung tissue. In addition, the increased number of alveolar macrophages associated with amiodarone administration has supported the concept that these cells may play a role in the pathogenesis of lung injury caused by amiodarone