Evidence map›Paper›PMID 32094214›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2020

Acetaminophen-Induced Liver Injury Alters Expression and Activities of Cytochrome P450 Enzymes in an Age-Dependent Manner in Mouse Liver.

Yifan Bao, Pei Wang, Xueyan Shao, Junjie Zhu, Jingcheng Xiao, Jian Shi, Lirong Zhang, Hao-Jie Zhu, Xiaochao Ma, José E Manautou and 1 more

Open access · bronzeAbstract read
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Article in Drug metabolism and disposition: the biological fate of chemicals, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
4.6field-weighted citation impact, top 5% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Article
  3. The Impact of Hyperuricemia on Pharmacokinetics in Sprague-Dawley Rats.European journal of drug metabolism and pharmacokinetics · 2025
    Article
  4. NAPQI is absent in the mouse brain after sub-hepatotoxic and hepatotoxic doses of acetaminophen.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Article
  5. Toxicological research · 2025
    Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Improved Detection of Drug-Induced Liver Injury by Integrating PredictedbioRxiv : the preprint server for biology · 2024
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Possible Role of Extracellular Vesicles in Hepatotoxicity of Acetaminophen.International journal of molecular sciences · 2022
    Article
  18. Roles of Cofactors in Drug-Induced Liver Injury: Drug Metabolism and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2022
    Review
  19. Article
  20. Withaferin A in the Treatment of Liver Diseases: Progress and Pharmacokinetic Insights.Drug metabolism and disposition: the biological fate of chemicals · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 2 countries.

Yifan BaoDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (Y.B., P.W., X.S., J.E.M., X.Z.); Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China (P.W., L.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (J.Z., X.M.); and Departments of Pharmaceutical Sciences (J.X.) and Clinical Pharmacy (J.S., H.-J.Z.), College of Pharmacy, University of Michigan, Ann Arbor, Michigan.
Pei WangDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (Y.B., P.W., X.S., J.E.M., X.Z.); Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China (P.W., L.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (J.Z., X.M.); and Departments of Pharmaceutical Sciences (J.X.) and Clinical Pharmacy (J.S., H.-J.Z.), College of Pharmacy, University of Michigan, Ann Arbor, Michigan.
Xueyan ShaoDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (Y.B., P.W., X.S., J.E.M., X.Z.); Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China (P.W., L.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (J.Z., X.M.); and Departments of Pharmaceutical Sciences (J.X.) and Clinical Pharmacy (J.S., H.-J.Z.), College of Pharmacy, University of Michigan, Ann Arbor, Michigan.
Junjie ZhuDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (Y.B., P.W., X.S., J.E.M., X.Z.); Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China (P.W., L.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (J.Z., X.M.); and Departments of Pharmaceutical Sciences (J.X.) and Clinical Pharmacy (J.S., H.-J.Z.), College of Pharmacy, University of Michigan, Ann Arbor, Michigan.
Jingcheng XiaoDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (Y.B., P.W., X.S., J.E.M., X.Z.); Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China (P.W., L.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (J.Z., X.M.); and Departments of Pharmaceutical Sciences (J.X.) and Clinical Pharmacy (J.S., H.-J.Z.), College of Pharmacy, University of Michigan, Ann Arbor, Michigan xiaobo.zhong@uconn.edu.
Jian ShiDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (Y.B., P.W., X.S., J.E.M., X.Z.); Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China (P.W., L.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (J.Z., X.M.); and Departments of Pharmaceutical Sciences (J.X.) and Clinical Pharmacy (J.S., H.-J.Z.), College of Pharmacy, University of Michigan, Ann Arbor, Michigan.
Lirong ZhangDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (Y.B., P.W., X.S., J.E.M., X.Z.); Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China (P.W., L.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (J.Z., X.M.); and Departments of Pharmaceutical Sciences (J.X.) and Clinical Pharmacy (J.S., H.-J.Z.), College of Pharmacy, University of Michigan, Ann Arbor, Michigan.
Hao-Jie ZhuDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (Y.B., P.W., X.S., J.E.M., X.Z.); Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China (P.W., L.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (J.Z., X.M.); and Departments of Pharmaceutical Sciences (J.X.) and Clinical Pharmacy (J.S., H.-J.Z.), College of Pharmacy, University of Michigan, Ann Arbor, Michigan.
Xiaochao MaDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (Y.B., P.W., X.S., J.E.M., X.Z.); Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China (P.W., L.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (J.Z., X.M.); and Departments of Pharmaceutical Sciences (J.X.) and Clinical Pharmacy (J.S., H.-J.Z.), College of Pharmacy, University of Michigan, Ann Arbor, Michigan xiaobo.zhong@uconn.edu.ORCID 0000-0003-2049-7467
José E ManautouDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (Y.B., P.W., X.S., J.E.M., X.Z.); Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China (P.W., L.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (J.Z., X.M.); and Departments of Pharmaceutical Sciences (J.X.) and Clinical Pharmacy (J.S., H.-J.Z.), College of Pharmacy, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-2503-9193
Xiao-Bo ZhongDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (Y.B., P.W., X.S., J.E.M., X.Z.); Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China (P.W., L.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (J.Z., X.M.); and Departments of Pharmaceutical Sciences (J.X.) and Clinical Pharmacy (J.S., H.-J.Z.), College of Pharmacy, University of Michigan, Ann Arbor, Michigan xiaobo.zhong@uconn.edu.ORCID 0000-0002-6537-5415
University of the Sciences · US

Funding

Genetic determinants of ACEI prodrug activationR01HL126969 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZHU, HAOJIE · 2016 to 2020
$1.9M
Pharmacoenhancers for antiretroviral therapy: safety and future developmentR01AI131983 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MA, XIAOCHAO · 2017 to 2021
$1.9M
Short- or long-term impacts of drug exposure at early life on drug metabolism, therapeutic efficacy, and drug-induced toxicityR01GM118367 · NIGMS · UNIVERSITY OF CONNECTICUT STORRS · PI ZHONG, XIAO-BO · 2016 to 2019
$1.2M
NHLBI NIH HHS R01 HL126969NIAID NIH HHS R01 AI131983NIGMS NIH HHS R01 GM118367
6 · The paper itself

Abstract

Drug-induced liver injury (DILI) is a global medical problem. The risk of DILI is often related to expression and activities of drug-metabolizing enzymes, especially cytochrome P450s (P450s). However, changes on expression and activities of P450s after DILI have not been determined. The aim of this study is to fill this knowledge gap. Acetaminophen (APAP) was used as a model drug to induce DILI in C57BL/6J mice at different ages of days 10 (infant), 22 (child), and 60 (adult). DILI was assessed by levels of alanine aminotransferase and aspartate aminotransferase in plasma with a confirmation by H&E staining on liver tissue sections. The expression of selected P450s at mRNA and protein levels was measured by real-time polymerase chain reaction and liquid chromatography-tandem mass spectrometry, respectively. The activities of these P450s were determined by the formation of metabolites from probe drugs for each P450 using ultraperformance liquid chromatography-quadrupole time of flight mass spectrometry. DILI was induced at mild to severe levels in a dose-dependent manner in 200, 300, and 400 mg/kg APAP-treated groups at child and adult ages, but not at the infant age. Significantly decreased expression at mRNA and protein levels as well as enzymatic activities of CYP2E1, 3A11, 1A2, and 2C29 were found at child and adult ages. Adult male mice were more susceptible to APAP-induced liver injury than female mice with more decreased expression of P450s. These results suggest that altered levels of P450s in livers severely injured by drugs may affect the therapeutic efficacy of drugs, which are metabolized by P450s, more particularly for males. SIGNIFICANCE STATEMENT: The current study in an animal model demonstrates that acetaminophen-induced liver injury results in decreased expression and enzyme activities of several examined drug-metabolizing cytochrome P450s (P450s). The extent of such decreases is correlated to the degree of liver injury severity. The generated data may be translated to human health for patients who have drug-induced liver injury with decreased capability to metabolize drugs by certain P450s.

Indexed as

AcetaminophenAdultAge FactorsAnimalsChemical and Drug Induced Liver InjuryChildCytochrome P-450 Enzyme SystemDisease Models, AnimalDose-Response Relationship, DrugFemaleGene Expression Regulation, EnzymologicHumansInfantLiverMaleMiceAcetaminophenCytochrome P-450 Enzyme SystemMidazolamOxazinesresorufin

Identifiers

PMID32094214
PMCPMC7153563
OpenAlexW3008843068

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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.