ArticleAntimicrobial agents and chemotherapy2016
Role of Inflammatory and Oxidative Stress, Cytochrome P450 2E1, and Bile Acid Disturbance in Rat Liver Injury Induced by Isoniazid and Lipopolysaccharide Cotreatment.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- [Gut microbiota-associated metabolites with drug-induced liver injury].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Isoniazid subverting erythrocyte homeostasis: implications for tuberculosis therapy.Frontiers in pharmacology · 2026Article
- Efficient analysis of drug interactions in liver injury: a retrospective study leveraging natural language processing and machine learning.BMC medical research methodology · 2024Article
- Breaking barriers: The potential of nanosystems in antituberculosis therapy.Bioactive materials · 2024Review
- Berberine Protects against High-Energy and Low-Protein Diet-Induced Hepatic Steatosis: Modulation of Gut Microbiota and Bile Acid Metabolism in Laying Hens.International journal of molecular sciences · 2023Article
- Hepatoprotective effect of hydromethanol extract ofMetabolism open · 2023Article
- Nutritional intervention is promising in alleviating liver injury during tuberculosis treatment: a review.Frontiers in nutrition · 2023Review
- Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: A review.Frontiers in pharmacology · 2022Review
- Valproic Acid-Induced Liver Injury: A Case-Control Study from a Prospective Pharmacovigilance Program in a Tertiary Hospital.Journal of clinical medicine · 2021Article
- Variations of Serum Oxidative Stress Biomarkers under First-Line Antituberculosis Treatment: A Pilot Study.Journal of personalized medicine · 2021Article
- Dietary Intake of Vegetables and Cooking Oil Was Associated With Drug-Induced Liver Injury During Tuberculosis Treatment: A Preliminary Cohort Study.Frontiers in nutrition · 2021Article
- What have we learned from animal models of idiosyncratic, drug-induced liver injury?Expert opinion on drug metabolism & toxicology · 2020Review
- A new perspective of triptolide-associated hepatotoxicity: the relevance of NF-Acta pharmaceutica Sinica. B · 2020Article
- Retinal astrocytes transcriptome reveals Cyp1b1 regulates the expression of genes involved in cell adhesion and migration.PloS one · 2020Article
- Hepatotoxicity Induced by Isoniazid-Lipopolysaccharide through Endoplasmic Reticulum Stress, Autophagy, and Apoptosis Pathways in Zebrafish.Antimicrobial agents and chemotherapy · 2019Article
- Preoperative short-term fasting protects liver injury in patients undergoing hepatectomy.Annals of translational medicine · 2018Article
- Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters.Disease markers · 2018Article
- Investigating the CYP2E1 Potential Role in the Mechanisms Behind INH/LPS-Induced Hepatotoxicity.Frontiers in pharmacology · 2018Article
- The pharmacogenomics of valproic acid.Journal of human genetics · 2017Review
- Isoniazid clearance is impaired among human immunodeficiency virus/tuberculosis patients with high levels of immune activation.British journal of clinical pharmacology · 2017Observational
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Isoniazid (INH) remains the core drug in tuberculosis management, but serious hepatotoxicity and potentially fatal liver injury continue to accompany INH consumption. Among numerous theories that have been established to explain INH-induced liver injury, an inflammatory stress theory has recently been widely used to explain the idiosyncrasy. Inflammatory stress usually sensitizes tissues to a drug's toxic consequences. Therefore, the present study was conducted to verify whether bacterial lipopolysaccharide (LPS)-induced inflammation may have a role in enhancing INH hepatotoxicity. While single INH or LPS administration showed no major toxicity signs, INH-LPS cotreatment intensified liver toxicity. Both blood biomarkers and histological evaluations clearly showed positive signs of severe liver damage accompanied by massive necrosis, inflammatory infiltration, and hepatic steatosis. Furthermore, elevated serum levels of bile acid associated with the repression of bile acid synthesis and transport regulatory parameters were observed. Moreover, the principal impact of cytochrome P450 2E1 (CYP2E1) on INH toxicity could be anticipated, as its protein expression showed enormous increases in INH-LPS-cotreated animals. Furthermore, the crucial role of CYP2E1 in the production of reactive oxygen species (ROS) was clearly obvious in the repression of hepatic antioxidant parameters. In summary, these results confirmed that this LPS-induced inflammation model might prove valuable in revealing the hepatotoxic mechanisms of INH and the crucial role played by CYP2E1 in the initiation and propagation of INH-induced liver damage, information which could be very useful to clinicians in understanding the pathogenesis of drug-induced liver injury.
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