AUTHOR=Pu Shiyun , Liu Qinhui , Li Yanping , Li Rui , Wu Tong , Zhang Zijing , Huang Cuiyuan , Yang Xuping , He Jinhan TITLE=Montelukast Prevents Mice Against Acetaminophen-Induced Liver Injury JOURNAL=Frontiers in Pharmacology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.01070 DOI=10.3389/fphar.2019.01070 ISSN=1663-9812 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.