ArticleFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association2016
Differential susceptibility to acetaminophen-induced liver injury in sub-strains of C57BL/6 mice: 6N versus 6J.
Article in Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Article
- Protein S-glutathionylation confers cellular resistance to ferroptosis induced by glutathione depletion.Redox biology · 2025Article
- The multiple mechanisms and modes of cell death after acetaminophen overdose.Exploration of digestive diseases · 2025Article
- The Discovery of Gut Microbial Metabolites as Modulators of Host Susceptibility to Acetaminophen-Induced Hepatotoxicity.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Deletion of Glyoxalase 1 Exacerbates Acetaminophen-Induced Hepatotoxicity in Mice.Antioxidants (Basel, Switzerland) · 2024Article
- Iguratimod, an allosteric inhibitor of macrophage migration inhibitory factor (MIF), prevents mortality and oxidative stress in a murine model of acetaminophen overdose.Molecular medicine (Cambridge, Mass.) · 2024Article
- Deletion of Glyoxalase 1 exacerbates acetaminophen-induced hepatotoxicity in mice.bioRxiv : the preprint server for biology · 2023Article
- Loss of microRNA-21 protects against acetaminophen-induced hepatotoxicity in mice.Archives of toxicology · 2023Article
- Metabolic differences and differentially expressed genes between C57BL/6J and C57BL/6N mice substrains.PloS one · 2022Article
- Recommendations for the use of the acetaminophen hepatotoxicity model for mechanistic studies and how to avoid common pitfalls.Acta pharmaceutica Sinica. B · 2021Review
- Supplier-origin mouse microbiomes significantly influence locomotor and anxiety-related behavior, body morphology, and metabolism.Communications biology · 2021Article
- Substrains matter in phenotyping of C57BL/6 mice.Experimental animals · 2021Review
- Immune-Mediated Drug-Induced Liver Injury: Immunogenetics and Experimental Models.International journal of molecular sciences · 2021Review
- Mitochondrial protein adduct and superoxide generation are prerequisites for early activation of c-jun N-terminal kinase within the cytosol after an acetaminophen overdose in mice.Toxicology letters · 2021Article
- Acetaminophen Test Battery (ATB): A Comprehensive Method to Study Acetaminophen-Induced Acute Liver Injury.Gene expression · 2020Review
- Mechanisms and pathophysiological significance of sterile inflammation during acetaminophen hepatotoxicity.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2020Review
- Medicinal Thiols: Current Status and New Perspectives.Mini reviews in medicinal chemistry · 2020Review
- Expression of mitochondrial membrane-linked SAB determines severity of sex-dependent acute liver injury.The Journal of clinical investigation · 2019Article
- Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats.Medicina (Kaunas, Lithuania) · 2019Article
- Animal models of drug-induced liver injury.Biochimica et biophysica acta. Molecular basis of disease · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
Abstract
Mouse models of acetaminophen (APAP) hepatotoxicity are considered relevant for the human pathophysiology. The C57BL/6 strain is most popular because it is the background strain of gene knock-out mice. However, conflicting results in the literature may have been caused by sub-strain mismatches, e.g. C57BL/6J and C57BL/6N. This study was initiated to determine the mechanism behind the sub-strain susceptibility to APAP toxicity. C57BL/6N and C57BL/6J mice were dosed with 200 mg/kg APAP and sacrificed at different time points. C57BL/6N mice developed significantly more liver injury as measured by plasma ALT activities and histology. Although there was no difference in glutathione depletion or cytochrome P450 activity between groups, C57BL/6N had a higher glutathione disulfide-to-glutathione ratio and more APAP protein adducts. C57BL/6N showed more mitochondrial translocation of phospho-JNK and BAX, and more release of mitochondrial intermembrane proteins apoptosis-inducing factor (AIF), second mitochondria-derived activator of caspases (SMAC), which caused more DNA fragmentation. The increased mitochondrial dysfunction was confirmed in vitro as C57BL/6N hepatocytes had a more precipitous drop in JC-1 fluorescence after APAP exposure.
conclusionC57BL/6N mice are more susceptible to APAP-induced hepatotoxicity, likely due to increased formation of APAP-protein adducts and a subsequent enhancement of mitochondrial dysfunction associated with aggravated nuclear DNA fragmentation.
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