ReviewDrug metabolism reviews2012
Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity.
Review in Drug metabolism reviews, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 405 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
405 citing papers in PubMed, 926 citations in OpenAlex.
- High Doses of N-Acetyl-P-Aminophenol Cause Acute Changes in Electroencephalographic and Electrocardiographic Activities in Wistar Rats.Basic & clinical pharmacology & toxicology · 2026Article
- Stimulation of OGG1 Enhances Oxidative DNA Damage Repair and Protects Against Acute Liver Failure by Acetaminophen.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Loss of Vacuole Membrane Protein 1 protects against acetaminophen-induced liver injury by modulating inflammation and hepatocyte proliferation.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Glutathione Biology in Neurodegenerative and Metabolic Diseases: Molecular Mechanisms, Pathophysiological Roles, and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Metal-drug coordinated nanozymes for ROS scavenging and Kupffer cell polarization to alleviate drug-induced liver injury.Acta pharmaceutica Sinica. B · 2026Article
- Article
- Ethanol as a Modifier of Drug Toxicity in Humans: Pathways of Toxicity and Organ-Level Consequences.International journal of molecular sciences · 2026Review
- TLR9-mediated innate immune signaling contributes to acetaminophen-induced injury in the developing lung.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- DNAJB4/HLJ1 protects against acetaminophen-induced liver injury by attenuating ER stress via HSP70.Cell biology and toxicology · 2026Article
- Hepatic supersulfides attenuate acetaminophen-induced liver injury via enhanced detoxification and anti-inflammatory mechanisms.Redox biology · 2026Article
- From In Vitro Genotoxicity Assays to Human Biomarkers: Interpreting DNA Damage Signals in Long-Term SSRI Therapy through a Translational Neurotoxicology Lens.Neurotoxicity research · 2026Review
- Dose- and Organ-Specific Dual Effects of MitoTempo in Paracetamol-Induced Hepatorenal Toxicity in Mice.Biomolecules · 2026Article
- Hepatotoxicity prediction for traditional Chinese medicine: a two-step in silico framework integrating network and machine learning approaches.BMC complementary medicine and therapies · 2026Article
- MALAT1 promotes acetaminophen-induced hepatocyte pyroptosis by stabilizing Rac1 through its interaction with MTDH and the hepatoprotective role of muniziqi saifula.Molecular and cellular biochemistry · 2026Article
- Single-cell transcriptomics of acetaminophen-induced responses in human 2D and 3D liver microtissues.Archives of toxicology · 2026Article
- The Difluoroboranyl-Fluoroquinolone Derivative "7a" Inhibits Bacterial DNA Gyrase and Exhibits Potent Activity Against Ciprofloxacin-ResistantMolecules (Basel, Switzerland) · 2026Article
- Targeting DNA fragment extrusion: a new therapeutic avenue for CClMolecular biology reports · 2026Article
- Metabolic heterogeneity, networks, and biomarkers of drug-induced liver injury.Journal of pharmaceutical analysis · 2026Article
- Hepatocyte-Specific MET Deletion Exacerbates Acetaminophen-Induced Hepatotoxicity in Mice.The American journal of pathology · 2026Article
- Binankadsurin A fromNutrients · 2026Article
345 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Hepatotoxicity is a serious problem during drug development and for the use of many established drugs. For example, acetaminophen overdose is currently the most frequent cause of acute liver failure in the United States and Great Britain. Evaluation of the mechanisms of drug-induced liver injury indicates that mitochondria are critical targets for drug toxicity, either directly or indirectly through the formation of reactive metabolites. The consequence of these modifications is generally a mitochondrial oxidant stress and peroxynitrite formation, which leads to structural alterations of proteins and mitochondrial DNA and, eventually, to the opening of mitochondrial membrane permeability transition (MPT) pores. MPT pore formation results in a collapse of mitochondrial membrane potential and cessation of adenosine triphosphate synthesis. In addition, the release of intermembrane proteins, such as apoptosis-inducing factor and endonuclease G, and their translocation to the nucleus, leads to nuclear DNA fragmentation. Together, these events trigger necrotic cell death. Alternatively, the release of cytochrome c and other proapoptotic factors from mitochondria can promote caspase activation and apoptotic cell death. Drug toxicity can also induce an inflammatory response with the formation of reactive oxygen species by Kupffer cells and neutrophils. If not properly detoxified, these extracellularly generated oxidants can diffuse into hepatocytes and trigger mitochondrial dysfunction and oxidant stress, which then induces MPT and necrotic cell death. This review addresses the formation of oxidants and the defense mechanisms available for cells and applies this knowledge to better understand mechanisms of drug hepatotoxicity, especially acetaminophen-induced liver injury.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.