Topotecan reduces sepsis‐induced acute lung injury and decreases the inflammatory response via the inhibition of the NF‐κB signaling pathway

Abstract

Abstract This study aims to determine the function of topotecan (TPT) in acute lung injury (ALI) induced by sepsis. The mouse sepsis model was constructed through cecal ligation and puncture (CLP). The ALI score and lung wet/dry (W/D) weight ratio were applied to evaluate the level of lung injury. Hematoxylin–eosin staining was used to examine the role of TPT in lung tissue in a CLP‐induced ALI mouse model. Enzyme‐linked immunosorbent assay and quantitative real‐time polymerase chain reaction were used to detect the concentrations of inflammatory factors, such as interleukin‐6 (IL‐6), IL‐1β, and tumor necrosis factor‐α. Western blot was used to detect relevant protein levels in the nuclear factor‐κB (NF‐κB) pathway. Moreover, 10‐day survival was recorded by constructing the CLP model. The results indicated that TPT could improve lung tissue damage in mice and could significantly reduce lung injury scores (p < 0.01) and the W/D ratio (p < 0.05). Treatment with ammonium pyrrolidinedithiocarbamate obtained the similar results with the TPT treatment. Both significantly reduced the inflammatory response in the lungs, including reducing the number of neutrophils and total cells in the bronchoalveolar lavage fluid (BALF), significantly reducing the total protein concentration of the BALF, and significantly inhibiting the activity of MPO. Both also inhibited inflammatory cytokine expression and the levels of NF‐κB pathway proteins induced by sepsis. Furthermore, TPT significantly improved survival in sepsis. TPT improves ALI in the CLP model by inhibiting the NF‐κB pathway, preventing fatal inflammation.

Keywords

• acute lung injury
• cecal ligation and puncture
• inflammation
• NF‐κB
• topotecan