Topotecan alleviates ventilator-induced lung injury via NF-κB pathway inhibition

Objective: We investigated the effect of topotecan on injury and inflammation in a model of ventilator-induced lung injury (VILI). Methods: Acute lung injury (ALI) was induced in mice by high-tidal volume ventilation, and the mice were then treated with topotecan or PBS. Lung tissue and bronchoalveolar lavage fluid were collected to assess pulmonary vascular leaks, inflammation, and cell apoptosis. Results: Compared to PBS treatment, topotecan significantly decreased the ALI score, myeloperoxidase (MPO) content, total protein concentration, and presence of inflammatory cells and inflammatory cytokines in bronchoalveolar lavage fluid. Topotecan also reduced caspase-3 activation and type II alveolar epithelial cell apoptosis. Moreover, topotecan inhibited NF-kappa B expression and activation in the VILI model. Conclusion: Topotecan alleviates acute lung injury in the model of VILI through the inhibition of the NF-kappa B pathway.