ArticleChemical research in toxicology2016
Chronic Treatment with Isoniazid Causes Protoporphyrin IX Accumulation in Mouse Liver.
Article in Chemical research in toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- NR1I2 genetic polymorphisms and the risk of anti-tuberculosis drug-induced hepatotoxicity: A systematic review and meta-analysis.Pharmacology research & perspectives · 2020Pooled it
- Natural Alkaloids Against Liver Injury: Mechanistic Insights and Multi-Target Therapeutic Potential.Biomolecules · 2026Review
- Cell-based approaches for the mechanistic understanding of drug-induced cholestatic liver injury.Archives of toxicology · 2025Review
- Comparison of Pyrazinamide with Isoniazid for Their Effects on the Heme Biosynthetic Pathway in Mouse Liver.Metabolites · 2025Article
- Roles of the ABCG2 Transporter in Protoporphyrin IX Distribution and Toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Roles ofFrontiers in genetics · 2024Article
- Protoporphyrin IX-induced phototoxicity: Mechanisms and therapeutics.Pharmacology & therapeutics · 2023Review
- A Review of Fatty Acid Biosynthesis Enzyme Inhibitors as Promising Antimicrobial Drugs.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Roles of Cofactors in Drug-Induced Liver Injury: Drug Metabolism and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: A review.Frontiers in pharmacology · 2022Review
- Clinical perspectives of isoniazid-induced liver injury.Liver research (Beijing, China) · 2021Review
- High-Performance Near-Infrared Fluorescent Secondary Antibodies for Immunofluorescence.Analytical chemistry · 2021Article
- Cell Type-Specific Roles of CD38 in the Interactions of Isoniazid with NADDrug metabolism and disposition: the biological fate of chemicals · 2020Article
- PXR-mediated idiosyncratic drug-induced liver injury: mechanistic insights and targeting approaches.Expert opinion on drug metabolism & toxicology · 2020Review
- Toxicoproteomic Profiling ofCells · 2020Article
- Results of a pilot study of isoniazid in patients with erythropoietic protoporphyria.Molecular genetics and metabolism · 2019Article
- The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury.Current pharmacology reports · 2018Article
- Deficiency of N-acetyltransferase increases the interactions of isoniazid with endobiotics in mouse liver.Biochemical pharmacology · 2017Article
- The Opportunities of Metabolomics in Drug Safety Evaluation.Current pharmacology reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Isoniazid (INH) can cause hepatotoxicity. In addition, INH is contraindicated in patients suffering from porphyrias. Our metabolomic analysis revealed that chronic treatment with INH in mice causes a hepatic accumulation of protoporphyrin IX (PPIX). PPIX is an intermediate in the heme biosynthesis pathway, and it is also known as a hepatotoxin. We further found that INH induces delta-aminolevulinate synthase 1 (ALAS1), the rate-limiting enzyme in heme biosynthesis. We also found that INH downregulates ferrochelatase (FECH), the enzyme that converts PPIX to heme. In summary, this study illustrated that chronic treatment with INH causes PPIX accumulation in mouse liver in part through ALAS1 induction and FECH downregulation. This study also highlights that drugs can disrupt the metabolic pathways of endobiotics and increase the risk of liver damage.
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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.