Bile-acid-induced cell injury and protection

Perez, Maria J; Briz, Oscar

doi:10.3748/wjg.15.1677

Cited by 717Drug Transport and Resistance MechanismsDrug-Induced Hepatotoxicity and ProtectionLiver physiology and pathology

Bile-acid-induced cell injury and protection

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Perez, Maria J, Briz, Oscar·2009·World Journal of Gastroenterology

DOI 10.3748/wjg.15.1677PMC PMC2668773

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Abstract

Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids (BAs) in cholestatic diseases. BAs may disrupt cell membranes through their detergent action on lipid components and can promote the generation of reactive oxygen species that, in turn, oxidatively modify lipids, proteins, and nucleic acids, and eventually cause hepatocyte necrosis and apoptosis. Several pathways are involved in triggering hepatocyte apoptosis. Toxic BAs can activate hepatocyte death receptors directly and induce oxidative damage, thereby causing mitochondrial dysfunction, and induce endoplasmic reticulum stress. When these compounds are taken up and accumulate inside biliary cells, they can also cause apoptosis. Regarding extrahepatic tissues, the accumulation of BAs in the systemic circulation may contribute to endothelial injury in the kidney and lungs. In gastrointestinal cells, BAs may behave as cancer promoters through an indirect mechanism involving oxidative stress and DNA damage, as well as acting as selection agents for apoptosis-resistant cells. The accumulation of BAs may have also deleterious effects on placental and fetal cells. However, other BAs, such as ursodeoxycholic acid, have been shown to modulate BA-induced injury in hepatocytes. The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis. Other natural BAs or their derivatives, such as cholyl-N-methylglycine or cholylsarcosine, have also aroused pharmacological interest owing to their protective properties.

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Bile acids can induce hepatocyte injury, mitochondrial damage, oxidative stress, DNA damage, and hepatocyte necrosis and apoptosis, which drive progression from NAFLD to NASH, fibrosis, and HCC.
“First, as strong hydrophobic detergents, bile acids can induce hepatocyte injury, mitochondrial damage, oxidative stress, DNA damage, and hepatocyte necrosis and apoptosis, all of which drive the progression of NAFLD to NASH, fibrosis and HCC (Audard et al., 2007; Perez and Briz, 2009).”
From Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis (2016) · cites this paper as Perez and Briz, 2009

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Authors: Perez, M. J., & Briz, O.
Venue: World Journal of Gastroenterology
Publisher: Baishideng Publishing Group Inc.
Published: 2009
Volume: 15
Issue: 14
Pages: 1677
ISSN: 1007-9327 (ISSN-L)
DOI: 10.3748/wjg.15.1677
PMC: PMC2668773
OpenAlex: W2124260053
Cited by: 717
References: 125
Citations by year: 2026: 59 · 2025: 50 · 2024: 42 · 2023: 45 · 2022: 63 · 2021: 61 · 2020: 45 · 2019: 52 · 2018: 53 · 2017: 51 · 2016: 31 · 2015: 31 · 2014: 30 · 2013: 32 · 2012: 23
FWCI: 2.10
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: World Journal of Gastroenterology (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: European Regional Development Fund (BFU2007-30688-E/BFI)
Topics: Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords: bile acids, hepatocyte injury, cholestasis, oxidative stress, reactive oxygen species, endoplasmic reticulum stress, mitochondrial dysfunction, death receptors, ursodeoxycholic acid, bile acid derivatives, glutathione, hepatoprotection
MeSH terms: Animals, Bile Acids and Salts, Biliary Tract Diseases, Cell Membrane, Cholestasis, Humans, Molecular Structure, Apoptosis, Oxidative Stress, Cytoprotection, Hepatocytes

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