The therapeutic effect of verapamil in lipopolysaccharide-induced acute lung injury

• Published in: Biochemical and biophysical research communications 2019-10, Vol.517 (4), p.648-654
• Main Authors: Song, Zhuohui, Li, Shufen, Zhang, Cuiying, Yuan, Li, Han, Lingna, Liu, Yan
• Format: Article
• Language: English
• Subjects: Acute lung injury; Inflammation; NF-κB; NLRP3; Verapamil
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.07.090

The objective of this study was to investigate the exact therapeutic effects of Verapamil on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the molecular mechanism involved, through using LPS-induced animal models as well as LPS-stimulated mouse primary peritoneal macrophages models. Our results demonstrated that Verapamil reduced LPS-induced pathological damage of the lung tissue, infiltration of inflammatory cells and the production of IL-1β, TNF-α, and MCP-1 in the serum. The MPO activity, MDA content, lung wet/dry ratio and LDH activity were also attenuated by Verapamil. In addition, Verapamil attenuated LPS-induced inflammatory cytokine production and oxidative stress in primary murine peritoneal macrophages in vitro. Moreover, we confirmed that NF-κB/NLRP3 pathway was involved in the therapeutic effect of Verapamil against LPS-induced injury in vivo and in vitro. In conclusion, these findings indicate that Verapamil has a therapeutic effect on LPS-induced ALI in mice. The mechanism may be related to the inhibition of NF-κB and NLRP3 signaling pathways. Verapamil may be a potential therapeutic agent for the treatment of ALI. •Verapamil ameliorates lung tissue injury in LPS-induced ALI mice.•Verapamil inhibits pro-inflammatory cytokine release and oxidative stress induced by LPS in primary macrophages.•NF-κB/NLRP3 pathway involved in the therapeutic effect of Verapamil against LPS-induced injury in vivo and in vitro.