Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury
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...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/3691701 |
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| author | Limei Wan Weibin Wu Shunjun Jiang Shanhe Wan Dongmei Meng Zhipeng Wang Jiajie Zhang Li Wei Pengjiu Yu |
| author_facet | Limei Wan Weibin Wu Shunjun Jiang Shanhe Wan Dongmei Meng Zhipeng Wang Jiajie Zhang Li Wei Pengjiu Yu |
| author_sort | Limei Wan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c81802c2c5de4ca5974a2b2f48051213 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-c81802c2c5de4ca5974a2b2f480512132025-02-03T05:57:51ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/36917013691701Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung InjuryLimei Wan0Weibin Wu1Shunjun Jiang2Shanhe Wan3Dongmei Meng4Zhipeng Wang5Jiajie Zhang6Li Wei7Pengjiu Yu8The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, ChinaDepartment of Basic Medicine, Zhaoqing Medical College, Zhaoqing 526020, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, ChinaRecent 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.http://dx.doi.org/10.1155/2020/3691701 |
| spellingShingle | Limei Wan Weibin Wu Shunjun Jiang Shanhe Wan Dongmei Meng Zhipeng Wang Jiajie Zhang Li Wei Pengjiu Yu Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury Mediators of Inflammation |
| title | Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury |
| title_full | Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury |
| title_fullStr | Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury |
| title_full_unstemmed | Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury |
| title_short | Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury |
| title_sort | mibefradil and flunarizine two t type calcium channel inhibitors protect mice against lipopolysaccharide induced acute lung injury |
| url | http://dx.doi.org/10.1155/2020/3691701 |
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