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Cited by 753Liver Disease Diagnosis and TreatmentMitochondrial Function and PathologyDrug-Induced Hepatotoxicity and Protection

The DOI matches its Crossref record; 346 of the 348 references it cites were found in a registry or an index.

Mitochondrial dysfunction in NASH: Causes, consequences and possible means to prevent it

Begriche, Karima, Igoudjil, Anissa, Pessayre, Dominique, Fromenty, Bernard·2006·Mitochondrion
DOI 10.1016/j.mito.2005.10.004
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Abstract

Calorie-enriched diet and lack of exercise are causing a worldwide surge of obesity, insulin resistance and lipid accretion in liver (i.e. hepatic steatosis), which can lead to steatohepatitis. Steatosis and nonalcoholic steatohepatitis (NASH) can also be induced by drugs such as amiodarone, tamoxifen and some antiretroviral drugs, including stavudine and zidovudine. There is accumulating evidence that mitochondrial dysfunction (more particularly respiratory chain deficiency) plays a key role in the physiopathology of NASH whatever its initial cause. In contrast, the mitochondrial beta-oxidation of fatty acids can be either increased (as in insulin resistance-associated NASH) or decreased (as in drug-induced NASH). However, in both circumstances, generation of reactive oxygen species (ROS) by the damaged respiratory chain can be augmented. ROS generation in an environment enriched in lipids in turn induces lipid peroxidation which releases highly reactive aldehydic derivatives (e.g. malondialdehyde) that have diverse detrimental effects on hepatocytes and other hepatic cells. In hepatocytes, ROS, reactive nitrogen species and lipid peroxidation products further impair the respiratory chain, either directly or indirectly through oxidative damage to the mitochondrial genome. This consequently leads to the generation of more ROS and a vicious cycle occurs. Mitochondrial dysfunction can also lead to apoptosis or necrosis depending on the energy status of the cell. ROS and lipid peroxidation products also increase the generation of several cytokines (TNF-alpha, TGF-beta, Fas ligand) playing a key role in cell death, inflammation and fibrosis. Recent investigations have shown that some genetic polymorphisms can significantly increase the risk of steatohepatitis and that several drugs can prevent or even reverse NASH. Interestingly, most of these drugs could exert their beneficial effects by improving directly or indirectly mitochondrial function in liver. Finding a drug, which could fully prevent oxidative stress and mitochondrial dysfunction in NASH is a major challenge for the next decade.

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346 of 346 references verified0 citation errors · 0 not checkable

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2 of the 348 references couldn’t be matched to a known paper.

Research works printed but not linked: 6

  1. Abbey-Toby, 2005, β-Aminoisobutyric acid alleviates steatohepatitis in a murine model of diabetes and obesity, Virchows Arch., 447, 305
  2. Begriche, 2005, A thymine catabolite, β-aminoisobutyric acid, reduces hepatic dysfunction and metabolic disorders in overweight or obese mice, J. Hepatol., 42, 243
  3. Fiorini, 2002, Primary non-function in steatotic livers is due to differential Toll-like expression and endotoxin sensitivity, Hepatology, 36, 198
  4. Haque, 2002, Nonalcoholic steatohepatitis (NASH) is associated with hepatocyte mitochondrial DNA depletion, Hepatology, 36, 403
  5. Igoudjil, 2005, Mitochondrial and metabolic disturbances induced by high dose of stavudine in mice are alleviated by coadministration of l-carnitine. Possible role of PPAR-α, J. Hepatol., 42, 247
  6. Sutton, 2003, The Ala-9Val dimorphism modulates the import of human manganese superoxide dismutase into rat liver mitochondria, Pharmacogentics, 13, 145, 10.1097/00008571-200303000-00004 · DOI

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Metadata

Authors
Begriche, K., Igoudjil, A., Pessayre, D., & Fromenty, B.
Affiliations
Inserm (FR)
Corresponding author
Fromenty, Bernard
ORCID
Venue
Mitochondrion
Publisher
Elsevier BV
Published
2006-02
Volume
6
Issue
1
Pages
1-28
ISSN
1567-7249 (ISSN-L)
DOI
10.1016/j.mito.2005.10.004
OpenAlex
W1978045299
Cited by
753
References
348
Citations by year
2026: 24 · 2025: 28 · 2024: 33 · 2023: 27 · 2022: 55 · 2021: 47 · 2020: 43 · 2019: 48 · 2018: 43 · 2017: 32 · 2016: 39 · 2015: 39 · 2014: 38 · 2013: 39 · 2012: 35
FWCI
4.46
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Mitochondrion (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
mitochondrial dysfunction, nonalcoholic steatohepatitis, hepatic steatosis, respiratory chain deficiency, reactive oxygen species, lipid peroxidation, malondialdehyde, mitochondrial DNA damage, insulin resistance, drug-induced liver injury, fatty acid beta-oxidation, apoptosis, cytokines, liver fibrosis, genetic polymorphism, oxidative stress
MeSH terms
Animals, Drug Therapy, Fatty Liver, Hepatitis, Humans, Mitochondria, Liver, Mitochondrial Diseases, Lipid Metabolism

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