ArticleToxicology2018
Mitochondrial dysfunction induced by leflunomide and its active metabolite.
Article in Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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
22 citing papers in PubMed, 51 citations in OpenAlex.
- Exploring DHODH inhibition with silibinin as a promising approach to treat drug resistance in epilepsy.Metabolic brain disease · 2026Article
- NK-A 17E-233I: a novel competitive inhibitor of human dihydroorotate dehydrogenase (DHODH) for cancer therapy.Journal of experimental & clinical cancer research : CR · 2025Article
- Mitochondria as a Disease-Relevant Organelle in Rheumatoid Arthritis: A Key Breakout in Fight Against the Disease.Biomedicines · 2025Review
- DFT Study of Interaction between Teriflunomide and β-cyclodextrin.Current molecular medicine · 2025Article
- Leflunomide Treatment Does Not Protect Neural Cells following Oxygen-Glucose Deprivation (OGD) In Vitro.Cells · 2024Article
- Teriflunomide treatment exacerbates cardiac ischemia reperfusion injury in isolated rat hearts.Cardiovascular drugs and therapy · 2023Article
- Treatment of rheumatoid arthritis with conventional, targeted and biological disease-modifying antirheumatic drugs in the setting of liver injury and non-alcoholic fatty liver disease.Rheumatology international · 2022Review
- Mitochondrial Dysfunction in Rheumatoid Arthritis.Biomolecules · 2022Review
- Article
- Poly ε-Caprolactone Nanoparticles for Sustained Intra-Articular Immune Modulation in Adjuvant-Induced Arthritis Rodent Model.Pharmaceutics · 2022Article
- Teriflunomide shifts the astrocytic bioenergetic profile from oxidative metabolism to glycolysis and attenuates TNFα-induced inflammatory responses.Scientific reports · 2022Article
- Rheumatoid arthritis and mitochondrial homeostasis: The crossroads of metabolism and immunity.Frontiers in medicine · 2022Review
- The Mitochondria-Independent Cytotoxic Effect of Leflunomide on RPMI-8226 Multiple Myeloma Cell Line.Molecules (Basel, Switzerland) · 2021Article
- Leflunomide an immunomodulator with antineoplastic and antiviral potentials but drug-induced liver injury: A comprehensive review.International immunopharmacology · 2021Review
- A mechanism of perhexiline's cytotoxicity in hepatic cells involves endoplasmic reticulum stress and p38 signaling pathway.Chemico-biological interactions · 2021Article
- Mitochondrial-LinkedFrontiers in immunology · 2021Article
- Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Natural products and other inhibitors of FEuropean journal of medicinal chemistry · 2020Review
- Mitochondrial dysfunction and apoptosis underlie the hepatotoxicity of perhexiline.Toxicology in vitro : an international journal published in association with BIBRA · 2020Article
- Selective Binding of Cyclodextrins with Leflunomide and Its Pharmacologically Active Metabolite Teriflunomide.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Leflunomide, an anti-inflammatory drug used for the treatment of rheumatoid arthritis, has been marked with a black box warning regarding an increased risk of liver injury. The active metabolite of leflunomide, A771726, which also carries a boxed warning about potential hepatotoxicity, has been marketed as teriflunomide for the treatment of relapsing multiple sclerosis. Thus far, however, the mechanism of liver injury associated with the two drugs has remained elusive. In this study, cytotoxicity assays showed that ATP depletion and subsequent LDH release were induced in a time- and concentration-dependent manner by leflunomide in HepG2 cells, and to a lesser extent, by A77 1726. The decline of cellular ATP levels caused by leflunomide was dramatically exacerbated when galactose was substituted for glucose as the sugar source, indicating a potential mitochondrial liability of leflunomide. By measuring the activities of immuno-captured mitochondrial oxidative phosphorylation (OXPHOS) complexes, we found that leflunomide and A77 1726 preferentially targeted complex V (F
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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.