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

Abstract

ObjectiveWe investigated the effect of topotecan on injury and inflammation in a model of ventilator-inducedlunginjury (VILI). MethodsAcute 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. ResultsCompared 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-κB expression and activation in the VILI model. ConclusionTopotecan alleviates acute lung injury in the model of VILI through the inhibition of the NF-κB pathway.