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

Cytokine. 2018 Oct:110:381-388. doi: 10.1016/j.cyto.2018.04.016. Epub 2018 May 24.

Abstract

Objective: We investigated the effect of topotecan on injury and inflammation in a model of ventilator-inducedlunginjury (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-κB expression and activation in the VILI model.

Conclusion: Topotecan alleviates acute lung injury in the model of VILI through the inhibition of the NF-κB pathway.

Keywords: Nuclear factor-kappa B (NF-κB); Topotecan; Ventilator-induced lung injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / metabolism*
  • Animals
  • Apoptosis / drug effects
  • Bronchoalveolar Lavage Fluid / chemistry
  • Caspase 3 / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism*
  • Peroxidase / metabolism
  • Topotecan / pharmacology*
  • Ventilator-Induced Lung Injury / drug therapy*
  • Ventilator-Induced Lung Injury / metabolism*

Substances

  • Cytokines
  • NF-kappa B
  • Topotecan
  • Peroxidase
  • Caspase 3