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

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,...

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Main Authors: Lucy Petagine, Hannah Everitt, Roy Sherwood, Daniel Gyamfi, Vinood B. Patel
Format: Article
Language:English
Published: Codon Publications 2022-05-01
Series:Journal of Renal and Hepatic Disorders
Subjects:
Online Access:http://mail.jrenhep.com/index.php/jrenhep/article/view/143
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author Lucy Petagine
Hannah Everitt
Roy Sherwood
Daniel Gyamfi
Vinood B. Patel
author_facet Lucy Petagine
Hannah Everitt
Roy Sherwood
Daniel Gyamfi
Vinood B. Patel
author_sort Lucy Petagine
collection DOAJ
description 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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spelling doaj.art-c94bbcc896394ae9bdb6029997b8421b2022-12-22T02:09:36ZengCodon PublicationsJournal of Renal and Hepatic Disorders2207-37442022-05-016110.15586/jrenhep.v6i1.143Time-Dependent Alterations in Liver Oxidative Stress due to Ethanol and AcetaldehydeLucy Petagine0Hannah Everitt1Roy Sherwood2Daniel Gyamfi3Vinood B. Patel4Centre for Nutraceuticals, School of Life Sciences, University of Westminster, London.Centre for Nutraceuticals, School of Life Sciences, University of Westminster, London.Department of Clinical Biochemistry, King’s College Hospital, London.The Doctors Laboratory Ltd, The Halo Building, 1 Mabledon Place, London WC1H 9AX, UK.Centre for Nutraceuticals, School of Life Sciences, University of Westminster, London; Department of Nutrition and Dietetics, King’s College London, London. 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. http://mail.jrenhep.com/index.php/jrenhep/article/view/143acetaldehydealcoholantioxidantapoptosismitochondriaoxidative stress
spellingShingle Lucy Petagine
Hannah Everitt
Roy Sherwood
Daniel Gyamfi
Vinood B. Patel
Time-Dependent Alterations in Liver Oxidative Stress due to Ethanol and Acetaldehyde
Journal of Renal and Hepatic Disorders
acetaldehyde
alcohol
antioxidant
apoptosis
mitochondria
oxidative stress
title Time-Dependent Alterations in Liver Oxidative Stress due to Ethanol and Acetaldehyde
title_full Time-Dependent Alterations in Liver Oxidative Stress due to Ethanol and Acetaldehyde
title_fullStr Time-Dependent Alterations in Liver Oxidative Stress due to Ethanol and Acetaldehyde
title_full_unstemmed Time-Dependent Alterations in Liver Oxidative Stress due to Ethanol and Acetaldehyde
title_short Time-Dependent Alterations in Liver Oxidative Stress due to Ethanol and Acetaldehyde
title_sort time dependent alterations in liver oxidative stress due to ethanol and acetaldehyde
topic acetaldehyde
alcohol
antioxidant
apoptosis
mitochondria
oxidative stress
url http://mail.jrenhep.com/index.php/jrenhep/article/view/143
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AT roysherwood timedependentalterationsinliveroxidativestressduetoethanolandacetaldehyde
AT danielgyamfi timedependentalterationsinliveroxidativestressduetoethanolandacetaldehyde
AT vinoodbpatel timedependentalterationsinliveroxidativestressduetoethanolandacetaldehyde