Alcoholic liver disease: Current insights into cellular mechanisms

Petagine, Lucy; Zariwala, Mohammed Gulrez; Patel, Vinood B.

doi:10.4331/wjbc.v12.i5.87

Cited by 21 publications

(14 citation statements)

References 117 publications

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Section: Discussionmentioning

confidence: 99%

“…Acute alcohol binge drinking is a major health issue (1,17). Alcohol has been shown to cause oxidative damage, increase ROS production as well as alter mitochondrial function and induce apoptosis (17). To date, limited studies have assessed the effects of both acute ethanol and acetaldehyde on oxidative damage and apoptosis in the liver over a 24-h period.…”

Section: Discussionmentioning

confidence: 99%

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Time-Dependent Alterations in Liver Oxidative Stress due to Ethanol and Acetaldehyde

Petagine

Everitt

Sherwood

et al. 2022

jrenhep

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Binge drinking is a major public health issue and ethanol-related liver insult may play a major role in the pathology of alcoholic liver disease. However, the degree of oxidative stress, cell death and contribution of acetaldehyde to liver damage over a 24-h period has yet to be determined. Herein, we aimed to investigate the effect of acute alcohol and elevated acetaldehyde levels on hepatic oxidative damage, apoptosis, and antioxidant enzyme activity over a 24-h period. Male Wistar rats were divided into four groups and animals were pre-injected (intraperitonially [i.p.]) with either saline (0.15 mol/L) or cyanamide (5-mmol/kg body weight), followed by either saline (0.15 mol/L) or ethanol (75-mmol/kg bodyweight). After 2.5, 6 and 24 h, hepatic cytosolic and mitochondrial fractions were analysed for indices of oxidative stress. At 2.5 h, cytosolic glutathione and malondialdehyde levels were significantly reduced and increased, respectively, with alcohol treatment. Caspase-3 activity and cytochrome c levels were increased with alcohol treatment at 24 h. The combination of cyanamide and alcohol treatment at 24 h led to a significant increase in serum alanine aminotransferase levels, and reduced albumin and total protein levels. Furthermore, glutathione peroxidase activity and glutathione reductase activity were significantly decreased and increased, respectively. Finally, superoxide dismutase activity was decreased in cytosol and increased in the mitochondria after cyanamide and ethanol treatment, respectively. This study indicates a complex differential effect of alcohol and acetaldehyde, whereby alcohol toxicity in the mitochondria takes place throughout the 24-h period, but raised acetaldehyde has a further detrimental effect on liver function.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Time-Dependent Alterations in Liver Oxidative Stress due to Ethanol and Acetaldehyde

Petagine

Everitt

Sherwood

et al. 2022

jrenhep

Self Cite

View full text Add to dashboard Cite

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“…Oxidative stress is essential for the assembly and activation of NLRP3 inflammasome [ 38 ]. In reaction to toxic compounds, KCs in the liver release a large amount of ROS [ 39 ], and damaged hepatocytes may also release ROS and DAMPs [ 40 ]. DAMPs cause the activation of the tumor necrosis factor receptor (TNFR), Toll-like receptors (TLR), and IL receptor 1, which in turn causes the signaling of the NLRP3 inflammasome [ 41 , 42 , 43 ].…”

Section: Noxs and Inflammasomes Activationmentioning

confidence: 99%

NOX as a Therapeutic Target in Liver Disease

2022

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The nicotinamide adenine dinucleotide phosphate hydrogen oxidase (NADPH oxidase or NOX) plays a critical role in the inflammatory response and fibrosis in several organs such as the lungs, pancreas, kidney, liver, and heart. In the liver, NOXs contribute, through the generation of reactive oxygen species (ROS), to hepatic fibrosis by acting through multiple pathways, including hepatic stellate cell activation, proliferation, survival, and migration of hepatic stellate cells; hepatocyte apoptosis, enhancement of fibrogenic mediators, and mediation of an inflammatory cascade in both Kupffer cells and hepatic stellate cells. ROS are overwhelmingly produced during malignant transformation and hepatic carcinogenesis (HCC), creating an oxidative microenvironment that can cause different and various types of cellular stress, including DNA damage, ER stress, cell death of damaged hepatocytes, and oxidative stress. NOX1, NOX2, and NOX4, members of the NADPH oxidase family, have been linked to the production of ROS in the liver. This review will analyze some diseases related to an increase in oxidative stress and its relationship with the NOX family, as well as discuss some therapies proposed to slow down or control the disease’s progression.

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“…A similar consideration can be made for alcohol, which is a common susceptibility factor for PCT development [ 77 ]. Alcohol is a hepatotoxin that generates toxic metabolites able to induce liver damage via different mechanisms such as oxidative stress, endotoxin production, impaired immunity, hypoxia, and endoplasmic-reticulum malfunction [ 78 ]. Interestingly, alcohol has been associated with hepcidin down-regulation via oxidative stress both in hepatoma cell lines and rodents [ 79 ], indicating another way for alcohol to trigger or enhance the clinical expression of PCT.…”

Section: Iron In Porphyria Cutanea Tardamentioning

confidence: 99%

Iron in Porphyrias: Friend or Foe?

2022

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Iron is a trace element that is important for many vital processes, including oxygen transport, oxidative metabolism, cellular proliferation, and catalytic reactions. Iron supports these functions mainly as part of the heme molecule. Heme synthesis is an eight-step process which, when defective at the level of one of the eight enzymes involved, can cause the development of a group of diseases, either inherited or acquired, called porphyrias. Despite the strict link between iron and heme, the role of iron in the different types of porphyrias, particularly as a risk factor for disease development/progression or as a potential therapeutic target or molecule, is still being debated, since contrasting results have emerged from clinical observations, in vitro studies and animal models. In this review we aim to deepen such aspects by drawing attention to the current evidence on the role of iron in porphyrias and its potential implication. Testing for iron status and its metabolic pathways through blood tests, imaging techniques or genetic studies on patients affected by porphyrias can provide additional diagnostic and prognostic value to the clinical care, leading to a more tailored and effective management.

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Alcoholic liver disease: Current insights into cellular mechanisms

Cited by 21 publications

References 117 publications

Time-Dependent Alterations in Liver Oxidative Stress due to Ethanol and Acetaldehyde

Time-Dependent Alterations in Liver Oxidative Stress due to Ethanol and Acetaldehyde

NOX as a Therapeutic Target in Liver Disease

Iron in Porphyrias: Friend or Foe?

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