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Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury
- Source :
- Mediators of Inflammation, Vol 2020 (2020)
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 09629351 and 14661861
- Volume :
- 2020
- Database :
- Directory of Open Access Journals
- Journal :
- Mediators of Inflammation
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.81802c2c5de4ca5974a2b2f48051213
- Document Type :
- article
- Full Text :
- https://doi.org/10.1155/2020/3691701