Evidence map›Paper›PMID 30858204›Full record

ArticleAntimicrobial agents and chemotherapy2019

Hepatotoxicity Induced by Isoniazid-Lipopolysaccharide through Endoplasmic Reticulum Stress, Autophagy, and Apoptosis Pathways in Zebrafish.

Yun Zhang, Juan Cen, Zhili Jia, Chung-Der Hsiao, Qing Xia, Xue Wang, Xiqiang Chen, Rongchun Wang, Zhenzhou Jiang, Luyong Zhang and 1 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2019. 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 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.1field-weighted citation impact, top 9% 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, 72 citations in OpenAlex.

  1. HBV/HCV coinfection and anti-tuberculosis drug-induced liver injury: from risk assessment and exploration of mechanisms to preventive considerations.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
    Review
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  5. Article
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  7. Lansoprazole Ameliorates Isoniazid-Induced Liver Injury.Pharmaceuticals (Basel, Switzerland) · 2024
    Article
  8. Evaluation of the hepatotoxicity ofFrontiers in pharmacology · 2024
    Article
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  13. Review
  14. Article
  15. Article
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  17. Cancers · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Yun ZhangBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province, People's Republic of China xiaohan_0818@163.com hliukch@sdas.org.ORCID 0000-0002-5060-1213
Juan CenKey Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, Henan Province, People's Republic of China.
Zhili JiaBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province, People's Republic of China.
Chung-Der HsiaoDepartment of Bioscience Technology, Chung Yuan Christian University, Chungli, Taiwan.
Qing XiaBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province, People's Republic of China.
Xue WangBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province, People's Republic of China.
Xiqiang ChenBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province, People's Republic of China.
Rongchun WangBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province, People's Republic of China.
Zhenzhou JiangJiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, People's Republic of China.
Luyong ZhangJiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, People's Republic of China.
Kechun LiuBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province, People's Republic of China xiaohan_0818@163.com hliukch@sdas.org.
Qilu University of Technology · CNChina Pharmaceutical University · CNChung Yuan Christian University · TWHenan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Isoniazid (INH) is a first-line antituberculosis drug. The incidence of adverse reactions accompanied by inflammation in the liver during drug administration to tuberculosis patients is high and severely affects clinical treatment. To better understand the mechanism of hepatotoxicity induced by INH under the inflammatory state, we compared the differences in levels of hepatotoxicity from INH between normal zebrafish and zebrafish in an inflammatory state to elucidate the hepatotoxic mechanism using different endpoints such as mortality, malformation, inflammatory effects, liver morphology, histological changes, transaminase analysis, and expression levels of certain genes. The results showed that the toxic effect of INH in zebrafish in an inflammatory state was more obvious than that in normal zebrafish, that liver size was significantly decreased as measured by liver fatty acid binding protein (LFABP) reporter fluorescence and intensity, and that alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly increased. Hematoxylin and eosin (HE) staining and electron microscopy showed that hepatocyte injury was more obvious in the inflammatory state. In the inflammatory state, INH significantly increased the expression levels of endoplasmic reticulum stress (ERS)-related factors (GRP78, ATF6, PERK, IRE1, XBP1s, GRP94, and CHOP), autophagy-related factors (beclin 1, LC3, Atg3, and Atg12), and apoptosis-related factors (caspase-3, caspase-8, caspase-9, Bax, p53, and Cyt) in larvae. Correlational analyses indicated that the transcription levels of the inflammatory factors interleukin-1b (IL-1b), tumor necrosis factor beta (TNF-β), cyclooxygenase 2 (COX-2), and TNF-ɑ were strongly positively correlated with ALT and AST. Furthermore, the ERS inhibitor sodium 4-phenylbutyrate (4-PBA) could ameliorate the hepatotoxicity of INH-lipopolysaccharide (LPS) in zebrafish larvae. These results indicated that INH hepatotoxicity was enhanced in the inflammatory state. ERS and its mediated autophagy and apoptosis pathways might be involved in INH-induced liver injury promoted by inflammation.

Indexed as

Alanine TransaminaseAnimalsAntitubercular AgentsApoptosisAspartate AminotransferasesEndoplasmic Reticulum StressFemaleIsoniazidLipopolysaccharidesLiverMaleOxidative StressReactive Oxygen SpeciesZebrafishAlanine TransaminaseAntitubercular AgentsAspartate AminotransferasesIsoniazidLipopolysaccharidesReactive Oxygen SpeciesapoptosisautophagyERSinflammatory stateisoniazidliver injuryzebrafish

Identifiers

PMID30858204
PMCPMC6496066
OpenAlexW2921353174

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.