Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury

Autor: Limei Wan, Weibin Wu, Shunjun Jiang, Shanhe Wan, Dongmei Meng, Zhipeng Wang, Jiajie Zhang, Li Wei, Pengjiu Yu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Mediators of Inflammation, Vol 2020 (2020)
Druh dokumentu: article
ISSN: 0962-9351
1466-1861
DOI: 10.1155/2020/3691701
Popis: Recent studies have illuminated that blocking Ca2+ influx into effector cells is an attractive therapeutic strategy for lung injury. We hypothesize that T-type calcium channel may be a potential therapeutic target for acute lung injury (ALI). In this study, the pharmacological activity of mibefradil (a classical T-type calcium channel inhibitor) was assessed in a mouse model of lipopolysaccharide- (LPS-) induced ALI. In LPS challenged mice, mibefradil (20 and 40 mg/kg) dramatically decreased the total cell number, as well as the productions of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). Mibefradil also suppressed total protein concentration in BALF, attenuated Evans blue extravasation, MPO activity, and NF-κB activation in lung tissue. Furthermore, flunarizine, a widely prescripted antimigraine agent with potent inhibition on T-type channel, was also found to protect mice against lung injury. These data demonstrated that T-type calcium channel inhibitors may be beneficial for treating acute lung injury. The important role of T-type calcium channel in the acute lung injury is encouraged to be further investigated.
Databáze: Directory of Open Access Journals
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