The DOI matches its Crossref record; 221 of the 221 references it cites were found in a registry or an index.
Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis
Abstract
The worldwide rising prevalence of obesity and insulin resistance is associated with a parallel increase in nonalcoholic fatty liver disease (NAFLD). NAFLD is characterized by excess accumulation of triglyceride in the hepatocyte due to increased inflow of free fatty acids and/or de novo lipogenesis caused by various drugs and multiple defects in energy metabolism. Accumulation of lipids in the hepatocyte impairs the oxidative capacity of the mitochondria, increasing the reduced state of the electron transport chain (ETC) complexes and stimulating peroxisomal and microsomal pathways of fat oxidation. The consequent increased generation of reactive oxygen species (ROS) and reactive aldehydic derivatives causes oxidative stress and cell death, via ATP, NAD, and glutathione depletion and DNA, lipid, and protein damage. Oxidative stress also triggers production of inflammatory cytokines, causing inflammation and a fibrogenic response. This ultimately results in the development of nonalcoholic steatohepatitis (NASH), which can result in end-stage liver disease. The current therapeutic strategies for NASH treatment are mostly directed toward correction of the risk factors. Stimulation of mitochondrial function may also prevent NASH development, protecting the cell against the increased flux of reduced substrates to the ETC and ROS generation.
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In the citing paper
“An increase in ROS generation can cause depletion of antioxidant enzymes (MnSOD, Catalase and glutathione peroxidase).”
From Intervention by picroside II on FFAs induced lipid accumulation and lipotoxicity in HepG2 cells (2021) · cites this paper as [9]
In the citing paper
“This leads to formation of lipid peroxides having detrimental effects on hepatocytes [9].”
From Intervention by picroside II on FFAs induced lipid accumulation and lipotoxicity in HepG2 cells (2021) · cites this paper as [9]
In the citing paper
“Several in vitro and in vivo studies, including the present one, have demonstrated an increase in the ROS production as a result of excess lipid accumulation within the hepatocytes [9].”
From Intervention by picroside II on FFAs induced lipid accumulation and lipotoxicity in HepG2 cells (2021) · cites this paper as [9]
In the citing paper
“Endogenous and exogenous AGEs provoke the initiation and progression of NAFLD.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [125]
In the citing paper
“The aggregation of AGEs decreases the levels of the most important cellular antioxidant peptides, glutathione (GSH), SIRT1, and tissue inhibitor of metalloproteinase 3 (TIMP3), accompanied by increased oxidative stress and inflammation, promoting inflammatory liver injury and fibrosis in experimental animal models and NAFLD patients55–57,124–126.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [125]
Citations
Cites
Free radicals in biology and medicine
Gutteridge, J. M. C. (1991) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(91)90478-o · Cited by 17,178
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207
Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes
Esterbauer, H., Schaur, R. J., & Zollner, H. (1991) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(91)90192-6 · Cited by 6,672
Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly
Beckman, J. S., & Koppenol, W. H. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.271.5.c1424 · Cited by 5,513
Leptin and the regulation of body weight in mammals
Friedman, J. M., & Halaas, J. L. (1998) · Nature · doi:10.1038/27376 · Cited by 5,405
Mitochondrial formation of reactive oxygen species
Turrens, J. F. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.049478 · Cited by 5,084
Adipokines in inflammation and metabolic disease
Ouchi, N., Parker, J. L., Lugus, J. J., & Walsh, K. (2011) · Nature Reviews Immunology · doi:10.1038/nri2921 · Cited by 4,625
Schafer, F. Q., & Buettner, G. R. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00480-4 · Cited by 4,587
Steatohepatitis: A tale of two “hits”?
Day, C. P., & James, O. F. W. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70599-2 · Cited by 4,285
Prevalence of Hepatic Steatosis in An Urban Population in the United States: Impact of Ethnicity
Browning, J. D., Szczepaniak, L. S., Dobbins, R., Nuremberg, P., Horton, J. D., Cohen, J. C., Grundy, S. M., & Hobbs, H. H. (2004) · Hepatology · doi:10.1002/hep.20466 · Cited by 3,664
Research works printed but not linked: 5
- Liochev, 1999, The relative importance of HO• and ONOO− in mediating the toxicity of O2•−, Free Radic. Biol. Med., 26, 777
- Seki, 2002, In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases, J. Hepatol., 37, 56, 10.1016/S0168-8278(02)00073-9 · DOI
- Seki, 2002, In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases, J. Hepatol., 37, 56, 10.1016/S0168-8278(02)00073-9 · DOI
- Phung, 2001, Vitamin E but not glutathione precursors inhibits hepatic fibrosis in experimental NASH exhibiting oxidative stress and mitochondrial abnormalities, Hepatology, 34, 361
- Hasegawa, 2001, Plasma transforming growth factor-beta1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study, Aliment. Pharmacol. Ther., 15, 10.1046/j.1365-2036.2001.01083.x · DOI
Cited by
Sorted by citations
Adipogenesis and metabolic health
Ghaben, A. L., & Scherer, P. E. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0093-z · Cited by 1,395
Brand, M. D. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.001 · Cited by 1,063
Decoding cell death signals in liver inflammation
Brenner, C., Galluzzi, L., Kepp, O., & Kroemer, G. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.03.033 · Cited by 1,022
Oxidative stress in obesity: A critical component in human diseases
Marseglia, L., Manti, S., D’Angelo, G., Nicotera, A., Parisi, E., Di Rosa, G., Gitto, E., & Arrigo, T. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms16010378 · Cited by 933
Triggering and resolution of inflammation in NASH
Schuster, S., Cabrera, D., Arrese, M., & Feldstein, A. E. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0009-6 · Cited by 943
Metadata
- Authors
- Rolo, A. P., Teodoro, J. S., & Palmeira, C. M.
- Affiliations
- University of Aveiro (PT)
- University of Coimbra (PT)
- Corresponding author
- Palmeira, Carlos M.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 52
- Issue
- 1
- Pages
- 59-69
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2061662539
- Cited by
- 955
- References
- 221
- Citations by year
- 2026: 39 · 2025: 51 · 2024: 56 · 2023: 73 · 2022: 58 · 2021: 74 · 2020: 68 · 2019: 75 · 2018: 73 · 2017: 66 · 2016: 67 · 2015: 70 · 2014: 78 · 2013: 76 · 2012: 27
- FWCI
- 6.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- nonalcoholic steatohepatitis, oxidative stress, non-alcoholic fatty liver disease, reactive oxygen species, mitochondrial dysfunction, electron transport chain, lipid accumulation, insulin resistance, obesity, inflammation, liver fibrosis, mitochondrial function, NAD+ depletion, glutathione depletion, end-stage liver disease
- MeSH terms
- Animals, DNA Damage, Fatty Acids, Nonesterified, Fatty Liver, Humans, Inflammation, Insulin Resistance, Mitochondria, Oxidation-Reduction, Triglycerides, Lipid Peroxidation, Cytokines, Reactive Oxygen Species, Oxidative Stress, Hepatocytes, Mice, Rats, Proteolysis, Non-alcoholic Fatty Liver Disease
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