Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity

doi:10.1016/0163-7258(95)00012-6

Pharmacology & Therapeutics

Volume 67, Issue 1, 1995, Pages 101-154

https://doi.org/10.1016/0163-7258(95)00012-6 Get rights and content

Abstract

Severe and prolonged impairment of mitochondrial β-oxidation leads to microvesicular steatosis, and, in severe forms, to liver failure, coma and death. Impairment of mitochondrial β-oxidation may be either genetic or acquired, and different causes may add their effects to inhibit β-oxidation severely and trigger the syndrome. Drugs and some endogenous compounds can sequester coenzyme A and/or inhibit mitochondrial β-oxidation enzymes (aspirin, valproic acid, tetracyclines, several 2-arylpropionate anti-inflammatory drugs, amineptine and tianeptine); they may inhibit both mitochondrial β-oxidation and oxidative phosphorylation (endogenous bile acids, amiodarone, perhexiline and diethylaminoethoxyhexestrol), or they may impair mitochondrial DNA transcription (interferon-α), 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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Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity

Abstract

Biochem. Pharmacol.

Am. J. Obstet. Gynecol.

FEBS Lett.

Biochim. Biophys. Acta

J. Pediatr.

Lancet

Mutat. Res.

J. Biol. Chem.

Arch. Biochem. Biophys.

Biochem. Pharmacol.

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Biochem. Pharmacol.

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Biochem. Biophys. Res. Commun.

Biochem. Pharmacol.

FEBS Lett.

Gastroenterology

Gastroenterology

Lancet

Toxicol. Appl. Pharmacol.

The effect of aspirin on valproic acid metabolism

Clin. Pharmacol. Ther.

Inhibition of hepatic microsomal cytochrome P-450-dependent monooxygenase reactions by fatty acyl-coenzyme A

Mol. Pharmacol.

A comparative trial of didanosine or zalcitabine after treatment with zidovudine in patients with human immunodeficiency virus infection

N. Engl. J. Med.

Sodium valproate and acute hepatic failure

Dev. Med. Child Neurol.

Association of a protein structure of probable membrane derivation with HeLa cell mtDNA near its origin of replication

Fatty liver: biochemical and clinical aspects

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J. Clin. Invest.

Oxidants, antioxidants, and the degenerative diseases of aging