ArticleChemical research in toxicology2013
Disruption of thioredoxin reductase 1 protects mice from acute acetaminophen-induced hepatotoxicity through enhanced NRF2 activity.
Article in Chemical research in toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 61 citations in OpenAlex.
- Comparative Study of Wild and CultivatedMolecules (Basel, Switzerland) · 2025Article
- Selenium and Skeletal Muscle Health in Sports Nutrition.Nutrients · 2025Review
- Nrf2 and Ferroptosis: Exploring Translational Avenues for Therapeutic Approaches to Neurological Diseases.Current drug targets · 2025Review
- Multitarget Pharmacology of Sulfur-Nitrogen Heterocycles: Anticancer and Antioxidant Perspectives.Antioxidants (Basel, Switzerland) · 2024Review
- c-Antioxidants & redox signaling · 2023Article
- High Density of NRF2 Expression in Malignant Cells Is Associated with Increased Risk of CNS Metastasis in Early-Stage NSCLC.Cancers · 2021Article
- Oxidative Stress in Cancer.Cancer cell · 2020Review
- Carveol a Naturally-Derived Potent and Emerging Nrf2 Activator Protects Against Acetaminophen-Induced Hepatotoxicity.Frontiers in pharmacology · 2020Article
- Article
- Design and synthesis of acetaminophen probe APAP-P1 for identification of the toxicity targets thioredoxin reductase-1 in HepaRG cells.RSC advances · 2019Article
- Signaling Pathways, Chemical and Biological Modulators of Nucleotide Excision Repair: The Faithful Shield against UV Genotoxicity.Oxidative medicine and cellular longevity · 2019Review
- Selenoprotein MsrB1 deficiency exacerbates acetaminophen-induced hepatotoxicity via increased oxidative damage.Archives of biochemistry and biophysics · 2017Article
- Purification, Preliminary Characterization and Hepatoprotective Effects of Polysaccharides from Dandelion Root.Molecules (Basel, Switzerland) · 2017Article
- The role of MAP2 kinases and p38 kinase in acute murine liver injury models.Cell death & disease · 2017Article
- Hepatoprotective Effect of Aqueous Extract from the Seeds of Orychophragmus violaceus against Liver Injury in Mice and HepG2 Cells.International journal of molecular sciences · 2017Article
- Research Resource: A Reference Transcriptome for Constitutive Androstane Receptor and Pregnane X Receptor Xenobiotic Signaling.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Schisandrol B protects against acetaminophen-induced acute hepatotoxicity in mice via activation of the NRF2/ARE signaling pathway.Acta pharmacologica Sinica · 2016Article
- Paradoxical Roles of Antioxidant Enzymes: Basic Mechanisms and Health Implications.Physiological reviews · 2016Review
- Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease.Free radical biology & medicine · 2015Review
- TrxR1 as a potent regulator of the Nrf2-Keap1 response system.Antioxidants & redox signaling · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
The critical importance of glutathione in mitigating the deleterious effects of electrophile generating drugs such as acetaminophen (APAP) is well established. However, the role of other antioxidant systems, such as that provided by thioredoxin, has not been extensively studied. Selenoprotein thioredoxin reductase 1 (Txnrd1) is important for attenuating activation of the apoptosis signaling-regulating kinase 1 (ASK1) and the c-Jun N-terminal kinase (JNK) pathway caused by high doses of APAP. Therefore, a detailed investigation of the role of Txnrd1 in APAP-induced hepatotoxicity was conducted. Liver-specific Txnrd1 knockout mice (Txnrd1(ΔLiv)) were generated and treated with a hepatotoxic dose (400 mg/kg) of APAP for 1 or 6 h. Liver toxicity was assessed by measuring the activities of liver enzymes aspartate aminotransferase and alanine aminotransferase in serum, in addition to histopathological analysis of liver sections and analysis of glutathione levels. At 1 h post-APAP treatment, total and mitochondrial glutathione levels in control and Txnrd1(ΔLiv) mice were similarly depleted. However, at 6 h post-APAP treatment, Txnrd1(ΔLiv) mice were resistant to APAP toxicity as liver enzymes and histology were not significantly different from the corresponding untreated mice. Analyses revealed the compensatory up-regulation of many of the nuclear factor erythroid 2-related factor 2 (NRF2) target genes and proteins in Txnrd1(ΔLiv) mice with and without APAP treatment. Yet, JNK was phosphorylated to a similar extent in APAP-treated control mice. The results suggest that Txnrd1(ΔLiv) mice are primed for xenobiotic detoxication primarily through NRF2 activation.
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.