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| Content Provider | frontiers |
|---|---|
| Author | Pu, Shiyun Liu, Qinhui Li, Yanping Li, Rui Wu, Tong Zhang, Zijing Huang, Cuiyuan Yang, Xuping He, Jinhan |
| Abstract | Acetaminophen (APAP) is a widely used over-the-counter antipyretic and analgesic drug. Overdose of APAP is the leading cause of hospital admission for acute liver failure. Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (Cysltr1), which protects from inflammation and oxidative stress. However, the function of montelukast in APAP-induced hepatotoxicity remains unknown. In this study, we examined whether pharmacological inhibition of Cystlr1 could protect mice against APAP-induced hepatic damage. We found that APAP treatment upregulated messenger RNA and protein levels of Cysltr1 both in vitro and in vivo. Pharmacological inhibition of Cysltr1 by montelukast ameliorated APAP-induced acute liver failure. The hepatoprotective effect of montelukast was associated with upregulation of hepatic glutathione/glutathione disulfide level, reduction in c-Jun-NH2-terminal kinase activation and oxidative stress. In mouse primary hepatocytes, inhibition of Cysltr1 by montelukast ameliorated the expression of inflammatory-related genes and APAP-induced cytotoxicity. We conclude that montelukast may be used to treat APAP-induced acute hepatic injury. |
| ISSN | 16639812 |
| DOI | 10.3389/fphar.2019.01070 |
| Volume Number | 10 |
| Journal | Frontiers in Pharmacology |
| Language | English |
| Publisher Date | 2019-09-18 |
| Access Restriction | Open |
| Subject Keyword | Montelukast Glutathione JNK Acetaminophen Cysteinyl leukotriene receptor 1 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Pharmacology (medical) |
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