UM  > 中華醫藥研究院
Acetaminophen-induced liver injury is attenuated in transgenic fat-1 mice endogenously synthesizing long-chain n-3 fatty acids
Feng, Ruibing1; Wang, Yang1; Liu, Conghui1; Yan, Chunyan2; Zhang, Hang2; Su, Huanxing1; Kang, Jing X.4; Shang, Chang-Zhen3; Wan, Jim-Bo1
2018-08
Source PublicationBIOCHEMICAL PHARMACOLOGY
ISSN0006-2952
Volume154Pages:75-88
Abstract

Acetaminophen (APAP) overdose-induced hepatotoxicity is the most commonly cause of drug-induced liver failure characterized by oxidative stress, mitochondrial dysfunction, and cell damage. Therapeutic efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFA) in several models of liver disease is well documented. However, the impacts of n-3 PUFA on APAP hepatotoxicity are not adequately addressed. In this study, the fat-1 transgenic mice that synthesize endogenous n-3 PUFA and wild type (WT) littermates were injected intraperitoneally with APAP at the dose of 400 mg/kg to induce liver injury, and euthanized at 0h, 2h, 4h and 6h post APAP injection for sampling. APAP overdose caused severe liver injury in WT mice as indicated by serum parameters, histopathological changes and hepatocyte apoptosis, which were remarkably ameliorated in fat-1 mice. These pro tective effects of n-3 PUFA were associated with regulation of the prolonged JNK activation via inhibition of apoptosis signal-regulating kinase 1 (ASKl)/mitogen-activated protein kinase kinase 4 (MKK4) pathway. Additionally, the augment of endogenous n-3 PUFA reduced nuclear factor kappa B (NF-kB) - mediated in flammation response induced by APAP treatment in the liver. These findings indicate that n-3 PUFA has potent protective effects against APAP-induced acute liver injury, suggesting that n-3 dietary supplement with n-3 PUFA may be a potential therapeutic strategy for the treatment of hepatotoxicity induced by APAP overdose.

KeywordAcetaminophen N-3 Polyunsaturated Fatty Acids Hepatotoxicity Jnk Inflammatory
DOI10.1016/j.bcp.2018.04.019
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000441369600008
PublisherPERGAMON-ELSEVIER SCIENCE LTD
The Source to ArticleWOS
Fulltext Access
Citation statistics
Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
3.Department of Hepatopancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
4.Laboratory for Lipid Medicine and Technology (LLMT), Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Feng, Ruibing,Wang, Yang,Liu, Conghui,et al. Acetaminophen-induced liver injury is attenuated in transgenic fat-1 mice endogenously synthesizing long-chain n-3 fatty acids[J]. BIOCHEMICAL PHARMACOLOGY,2018,154:75-88.
APA Feng, Ruibing.,Wang, Yang.,Liu, Conghui.,Yan, Chunyan.,Zhang, Hang.,...&Wan, Jim-Bo.(2018).Acetaminophen-induced liver injury is attenuated in transgenic fat-1 mice endogenously synthesizing long-chain n-3 fatty acids.BIOCHEMICAL PHARMACOLOGY,154,75-88.
MLA Feng, Ruibing,et al."Acetaminophen-induced liver injury is attenuated in transgenic fat-1 mice endogenously synthesizing long-chain n-3 fatty acids".BIOCHEMICAL PHARMACOLOGY 154(2018):75-88.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Feng, Ruibing]'s Articles
[Wang, Yang]'s Articles
[Liu, Conghui]'s Articles
Baidu academic
Similar articles in Baidu academic
[Feng, Ruibing]'s Articles
[Wang, Yang]'s Articles
[Liu, Conghui]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Feng, Ruibing]'s Articles
[Wang, Yang]'s Articles
[Liu, Conghui]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.