The role of mast cells and macrophages in amiodarone induced pulmonary fibrosis and the possible attenuating role of atorvastatin

Abstract

Amiodarone (AM) is an effective anti-arrhythmic drug. We investigated the role of mast cells and macrophages on AM induced pulmonary fibrosis and the action of atorvastatin on this fibrosis. Rats were allocated into four groups; negative control (1), positive control (2), 30 mg/kg body weight/day AM (3) and AM + 10 mg/kg/day atorvastatin (4). Lungs were harvested and prepared for histology and immunohistochemistry. Hematoxylin and eosin stained sections of group 3 exhibited disorganized lung architecture. We found cellular debris in the lumen of both intrapulmonary bronchi and bronchioles with partial disruption of the thickened epithelial lining and mononuclear cellular infiltration into the lamina propria. We also observed thickening of the epithelial lining and the smooth muscle layer. Congested, dilated and thickened blood capillaries and thickened inter-alveolar septa were observed with mononuclear cellular infiltrates in the lung of group 3. Most alveoli were collapsed, but some dilated ones were detected. In some alveoli, type ІІ pneumocytes were increased, while type I cells were decreased. We observed significant increases in the amount of collagen in the thickened inter-alveolar septa, around bronchioles and around blood capillaries in sections from group 3. We found a significant increase in mast cells and alveolar macrophages in group 3 compared to group 1. Mast cells and macrophages appear to play important roles in AM induced pulmonary fibrosis. Atorvastatin appears to attenuate this condition.