ArticleAntioxidants & redox signaling2013
An indole derivative protects against acetaminophen-induced liver injury by directly binding to N-acetyl-p-benzoquinone imine in mice.
Article in Antioxidants & redox signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- [Gut microbiota-associated metabolites with drug-induced liver injury].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Sesamin alleviates drug-induced hepatotoxicity via autophagy enhancement and ferroptosis inhibition.Redox report : communications in free radical research · 2025Article
- Oxindole derivatives alleviate paracetamol-induced nephrotoxicity and hepatotoxicity: biochemical, histological, and computational expressions.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- 6-Hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline Demonstrates Anti-Inflammatory Properties and Reduces Oxidative Stress in Acetaminophen-Induced Liver Injury in Rats.Current issues in molecular biology · 2023Article
- Protective Effects of Apamin on Acetaminophen-Induced Hepatotoxicity in Mice.Current issues in molecular biology · 2023Article
- Sesamin Protects against APAP-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Inflammatory Response via Deactivation of HMGB1/TLR4/NFJournal of immunology research · 2023Article
- Alleviation of hippocampal necroptosis and neuroinflammation by NecroX-7 treatment after acute seizures.Frontiers in pharmacology · 2023Article
- Is Glyceryl Trinitrate, a Nitric Oxide Donor Responsible for Ameliorating the Chemical-Induced Tissue Injury In Vivo?Molecules (Basel, Switzerland) · 2022Article
- CYP2E1 inhibition and NF_κB Signaling Pathway are Involved in the Protective Molecular Effect ofIranian journal of pharmaceutical research : IJPR · 2021Article
- SIRT3 promotes antimycobacterial defenses by coordinating mitochondrial and autophagic functions.Autophagy · 2019Article
- Article
- Generation of small molecules to interfere with regulated necrosis.Cellular and molecular life sciences : CMLS · 2016Review
- The Free Radical Scavenger NecroX-7 Attenuates Acute Graft-versus-Host Disease via Reciprocal Regulation of Th1/Regulatory T Cells and Inhibition of HMGB1 Release.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Therapeutic efficacy of Wuzhi tablet (Schisandra sphenanthera Extract) on acetaminophen-induced hepatotoxicity through a mechanism distinct from N-acetylcysteine.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsAcetaminophen (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.
resultsNecroX-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.
conclusionOur 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.
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