Lung injury following inhaled chemotherapy

Objective: We evaluated lung injury following inhaled treatment with paclitaxel, and determined the potential mechanism underlying the lung injury and remodeling following inhaled treatment. Methods: Sprague-Dawley rats were treated with paclitaxel (3 mg/kg), via tracheal intubation and mechanical aeration. Histopathological changes in lung tissue were determined by haematoxylin and eosin staining. In addition, activity of matrix MMP-2 and MMP-9 was measured by gelatin zymography. Results: Significant lung injury was found in paclitaxel-treated rats of ≥ 3 mg/kg group, P<0.05. In contrast, lung injury was mild in<3 mg/kg group. Activity of MMP-9 and MMP-2 in lung tissue was significantly increased in all rats received inhaled treatment, P<0.05. However, the magnitude of increase was greater in ≥ 3 mg/kg paclitaxel-treated group compared to<3 mg/kg groups. In addition, the increase of MMP-9 activity appeared to be time-dependently suppressed, whereas the increase of MMP-2 activity was time-dependent exacerbated. Conclusion: Inhaled chemotherapy with paclitaxel at dose 3 mg/kg and over may lead to significant lung injury. MMP-9 may play important role in lung injury, whereas MMP-2 may play important role in lung remodeling following inhaled treatment.