ArticlePloS one2020
Cell-permeable succinate prodrugs rescue mitochondrial respiration in cellular models of acute acetaminophen overdose.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Mitochondrial remodeling after conventional and ultra-high dose rate irradiation in head and neck carcinoma cells in vitro.Clinical and translational radiation oncology · 2026Article
- Optical and Microdialysis Monitoring of Succinate Prodrug Treatment in a Rotenone-Induced Model of Mitochondrial Dysfunction in Swine.Metabolites · 2026Article
- Acute CClJournal of bioenergetics and biomembranes · 2025Article
- Dose-dependent effects of acetaminophen and ibuprofen on mitochondrial respiration of human platelets.Molecular and cellular biochemistry · 2024Article
- Assessing Platelet Mitochondrial Dysfunction in a Murine Model of Acute Acetaminophen Toxicity.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2023Article
- Succinate prodrugs in combination with atropine and pralidoxime protect cerebral mitochondrial function in a rodent model of acute organophosphate poisoning.Scientific reports · 2022Article
- Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Amiodarone Toxicity.International journal of molecular sciences · 2021Article
- Oxidant Stress and Acetaminophen Hepatotoxicity: Mechanism-Based Drug Development.Antioxidants & redox signaling · 2021Article
- Article
- Emerging cellular-based therapies in carbon monoxide poisoning.American journal of physiology. Cell physiology · 2021Review
- Improvement of Platelet Respiration by Cell-Permeable Succinate in Diabetic Patients Treated with Statins.Life (Basel, Switzerland) · 2021Article
- Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Statin Toxicity.International journal of molecular sciences · 2021Article
- Leigh Syndrome: A Tale of Two Genomes.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acetaminophen is one of the most common over-the-counter pain medications used worldwide and is considered safe at therapeutic dose. However, intentional and unintentional overdose accounts for up to 70% of acute liver failure cases in the western world. Extensive research has demonstrated that the induction of oxidative stress and mitochondrial dysfunction are central to the development of acetaminophen-induced liver injury. Despite the insight gained on the mechanism of acetaminophen toxicity, there still is only one clinically approved pharmacological treatment option, N-acetylcysteine. N-acetylcysteine increases the cell's antioxidant defense and protects liver cells from further acetaminophen-induced oxidative damage. Because it primarily protects healthy liver cells rather than rescuing the already injured cells alternative treatment strategies that target the latter cell population are warranted. In this study, we investigated mitochondria as therapeutic target for the development of novel treatment strategies for acetaminophen-induced liver injury. Characterization of the mitochondrial toxicity due to acute acetaminophen overdose in vitro in human cells using detailed respirometric analysis revealed that complex I-linked (NADH-dependent) but not complex II-linked (succinate-dependent) mitochondrial respiration is inhibited by acetaminophen. Treatment with a novel cell-permeable succinate prodrug rescues acetaminophen-induced impaired mitochondrial respiration. This suggests cell-permeable succinate prodrugs as a potential alternative treatment strategy to counteract acetaminophen-induced liver injury.
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