Loading...
Please wait, while we are loading the content...
Similar Documents
An Indole Derivative Protects Against Acetaminophen-Induced Liver Injury by Directly Binding to N-Acetyl-p-Benzoquinone Imine in Mice
| Content Provider | PubMed Central |
|---|---|
| Author | Park, Ji-hoon Seo, Kang-sik Surendar, Tadi Ahn, Bong-hyun Lee, Jung-uee Heo, Jun-young Han, Jeongsu Song, Myoung-sub Kim, Soon-ha Yim, Yong-hyeon Choi, Hueng-sik Shong, Minho Kweon, Giryang |
| Copyright Year | 2013 |
| Abstract | Aims: Acetaminophen (APAP)-induced liver injury is mainly due to the excessive formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) through the formation of a reactive intermediate, N-acetyl-p-benzoquinone imine (NAPQI), in both humans and rodents. Here, we show that the indole-derived synthetic compound has a protective effect against APAP-induced liver injury in C57Bl/6 mice model. Results: NecroX-7 decreased tert-butylhydroperoxide (t-BHP)- and APAP-induced cell death and ROS/RNS formation in HepG2 human hepatocarcinoma and primary mouse hepatocytes. In mice, NecroX-7 decreased APAP-induced phosphorylation of c-Jun N-terminal kinase (JNK) and 3-nitrotyrosine (3-NT) formation, and also protected mice from APAP-induced liver injury and lethality by binding directly to NAPQI. The binding of NecroX-7 to NAPQI did not require any of cofactors or proteins. NecroX-7 could only scavenge NAPQI when hepatocellular GSH levels were very low. Innovation: NecroX-7 is an indole-derived potent antioxidant molecule, which can be bound to some types of radicals and especially NAPQI. It is well known that the NAPQI is a major intermediate of APAP, which causes necrosis of hepatocytes in rodents and humans. Thus, blocking NAPQI formation or eliminating NAPQI are novel strategies for the treatment or prevention of APAP-induced liver injury instead of GSH replenishment. Conclusion: Our data suggest that the indole-derivative, NecroX-7, directly binds to NAPQI when hepatic GSH levels are very low and the NAPQI–NecroX-7 complex is secreted to the blood from the liver. NecroX-7 shows more preventive and similar therapeutic effects against APAP-induced liver injury when compared to the effect of N-acetylcysteine in C57Bl/6 mice. Antioxid. Redox Signal. 18, 1713–1722. |
| Related Links | http://dx.doi.org/10.1089/ars.2012.4677 |
| Ending Page | 1722 |
| Page Count | 10 |
| Starting Page | 1713 |
| File Format | |
| ISSN | 15577716 |
| e-ISSN | 15577716 |
| Journal | Antioxidants & Redox Signaling |
| Issue Number | 14 |
| Volume Number | 18 |
| Language | English |
| Publisher | Mary Ann Liebert, Inc. |
| Access Restriction | Open |
| Rights Holder | Mary Ann Liebert, Inc. |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Physiology Medicine Molecular Biology Clinical Biochemistry Biochemistry |
