Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity
Abstract
Severe and prolonged impairment of mitochondrial beta-oxidation leads to microvesicular steatosis, and, in severe forms, to liver failure, coma and death. Impairment of mitochondrial beta-oxidation may be either genetic or acquired, and different causes may add their effects to inhibit beta-oxidation severely and trigger the syndrome. Drugs and some endogenous compounds can sequester coenzyme A and/or inhibit mitochondrial beta-oxidation enzymes (aspirin, valproic acid, tetracyclines, several 2-arylpropionate anti-inflammatory drugs, amineptine and tianeptine); they may inhibit both mitochondrial beta-oxidation and oxidative phosphorylation (endogenous bile acids, amiodarone, perhexiline and diethylaminoethoxyhexestrol), or they may impair mitochondrial DNA transcription (interferon-alpha), or decrease mitochondrial DNA replication (dideoxynucleoside analogues), while other compounds (ethanol, female sex hormones) act through a combination of different mechanisms. Any investigational molecule should be screened for such effects.
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Excess hepatic FFAs overload alters the process of β-oxidation, increasing the flow of reducing equivalents NADH and FADH2 across the ETC.
“Excess of hepatic FFAs overload alters the process of β-oxidation, increasing the flow of reducing equivalents NADH and FADH2 across ETC [38].”
From Intervention by picroside II on FFAs induced lipid accumulation and lipotoxicity in HepG2 cells (2021) · cites this paper as [38]
Complexes I and III are the major sites for superoxide formation.
“since they are the major sites for superoxide formation [[36], [37], [38], [39], [40], [41]].”
From Intervention by picroside II on FFAs induced lipid accumulation and lipotoxicity in HepG2 cells (2021) · cites this paper as [38]
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“Excess of hepatic FFAs overload alters the process of b-oxidation, increasing the flow of reducing equivalents NADH and FADH2 across ETC [38].”
BackgroundInfluential
- Authors
- Fromenty, B., & Pessayre, D.
- Affiliations
- Inserm (FR)
- Corresponding author
- Fromenty, Bernard
- ORCID
- Fromenty, Bernard
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 1995-01
- Volume
- 67
- Issue
- 1
- Pages
- 101-154
- ISSN
- 0163-7258 (ISSN-L)
- OpenAlex
- W2016716965
- Cited by
- 665
- References
- 9
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 20 · 2023: 21 · 2022: 25 · 2021: 16 · 2020: 24 · 2019: 24 · 2018: 33 · 2017: 31 · 2016: 30 · 2015: 29 · 2014: 30 · 2013: 28 · 2012: 31
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- mitochondrial beta-oxidation, hepatotoxicity, microvesicular steatosis, drug-induced liver injury, oxidative phosphorylation inhibition, mitochondrial transcription, mitochondrial DNA replication, aspirin, valproic acid, tetracycline, amineptine, tianeptine, amiodarone, perhexiline, interferon-alpha, ethanol, female sex hormones, liver failure
- MeSH terms
- Ethanol, Animals, Anti-Inflammatory Agents, Anti-Bacterial Agents, Bile Acids and Salts, DNA Replication, DNA, Mitochondrial, Electron Transport, Fat Necrosis, Fatty Liver, Female, Hormones, Humans, Liver Diseases, Metabolism, Inborn Errors, Mitochondria, Liver, Oxidation-Reduction, Oxidative Phosphorylation, Pregnancy, Pregnancy Complications, Reye Syndrome, Chemical and Drug Induced Liver Injury
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