The effect of acute alcohol exposure on hepatic oxidative stress and function: prevention by micronutrients

Everitt, H.E. 2010. The effect of acute alcohol exposure on hepatic oxidative stress and function: prevention by micronutrients. PhD thesis University of Westminster School of Life Sciences

TitleThe effect of acute alcohol exposure on hepatic oxidative stress and function: prevention by micronutrients
TypePhD thesis
AuthorsEveritt, H.E.
Abstract

Alcohol binge drinking, especially in teenagers and young adults is a major

public health issue in the UK, with the number of alcohol related liver disorders steadily increasing. Understanding the mechanisms behind liver disease

arising from binge-drinking and finding ways to prevent such damage are

currently important areas of research. In the present investigation the effect of acute ethanol administration on hepatic oxidative damage and apoptosis was

examined using both an in vivo and in vitro approach; the effect of micronutrient supplementation prior and during ethanol exposure was also studied. The

following studies were performed: (1) ethanol administration (75 mmol/kg body

weight) and cyanamide pre-treatment followed by ethanol to study elevated

acetaldehyde levels with liver tissue analysed 2.5, 6 and 24 hours post-alcohol; (2). Using juvenile animals, 2% betaine supplementation followed by acute

ethanol with tissue analysed 24 hrs post ethanol; and (3). Micronutrient

supplementation during concomitant ethanol exposure to hepG2 cells. It was

found that a single dose of alcohol caused oxidative damage to the liver of rats at 2.5 hr post-alcohol as evidenced by decreased glutathione levels and

increased malondialdehyde levels in both the cytosol and mitochondria. Liver

function was also depressed but there were no findings of apoptosis as

cytochrome c levels and caspase 3 activity was unchanged. At 6 hours, the

effect of ethanol was reduced suggesting some degree of recovery, however,

by 24 hours, increased mitochondrial oxidative stress was apparent. The effect

of elevated acetaldehyde on hepatic damage was particularly evident at 24

hours, with some oxidative changes at earlier time points. At 24 hours,

acetaldehyde caused a profound drop in glutathione levels in the cytosol and

hepatic function was still deteriorating. Studies examining ethanol exposure to

juvenile livers showed that glutathione levels were increased, suggesting an

overtly protective response not seen in with older animals. It also showed that

despite cytochrome c release into the cytosol, caspase-3 levels were not

increased. This suggests that ATP depletion is preventing apoptosis initiation.

Betaine supplementation prevented almost all of the alcohol-mediated changes,

suggesting that the main mechanism behind alcohol-mediated liver damage is

oxidative stress. Results using the hepG2 cell line model showed that

micronutrients involved in glutathione synthesis can protect against hepatocyte

damage caused by alcohol metabolism, with reduced reactive oxygen species

and increased/maintained glutathione levels. In summary, these results

demonstrate that both acute alcohol and acetaldehyde can have damaging

effects to the liver, but that dietary intervention may be able to protect against ethanol induced oxidative stress.

Year2010
Publication dates
Completed2010

Related outputs

Time-Dependent Alterations in Liver Oxidative Stress due to Ethanol and Acetaldehyde
Petagine, L., Everitt, H.E., Sherwood, R., Gyamfi, D. and Patel, V.B. 2022. Time-Dependent Alterations in Liver Oxidative Stress due to Ethanol and Acetaldehyde. Journal of Renal and Hepatic Disorders. 6 (1), pp. 56-66. https://doi.org/10.15586/jrenhep.v6i1.143

Acute alcohol tissue damage: Protective properties of betaine
Petagine, L., Everitt, H.E., Preedy, V.R., Sherwood, R. and Patel, V. 2021. Acute alcohol tissue damage: Protective properties of betaine. Journal of Renal and Hepatic Disorders. 5 (1). https://doi.org/10.15586/jrenhep.v5i1.96

Acute Alcohol Tissue Damage: Protective Properties of Betaine
Petagine, L., Everitt, H.E., Preedy, V.R., Sherwood, R. and Patel, V.B. 2021. Acute Alcohol Tissue Damage: Protective Properties of Betaine. Journal of Renal and Hepatic Disorders. 5 (1), pp. 19-29. https://doi.org/10.15586/jrenhep.v5i1.96

Hepatic mitochondrial dysfunction induced by fatty acids and ethanol
Gyamfi, D., Everitt, H.E., Tewfik, I., Clemens, D.L. and Patel, V. 2012. Hepatic mitochondrial dysfunction induced by fatty acids and ethanol. Free Radical Biology & Medicine. 53 (11), pp. 2131-2145. https://doi.org/10.1016/j.freeradbiomed.2012.09.024

Chinese herbal products in the prevention and treatment of liver disease
Gyamfi, D., Everitt, H.E. and Patel, V. 2012. Chinese herbal products in the prevention and treatment of liver disease. in: Watson, R.R. and Preedy, V.R. (ed.) Bioactive food as dietary interventions for liver and gastrointestinal disease Academic Press. pp. 537-550

Apoptosis in alcoholic liver disease
Gyamfi, D., Everitt, H.E. and Patel, V. 2010. Apoptosis in alcoholic liver disease. in: Preedy, V.R. (ed.) Apoptosis: modern insights into disease from molecules to man Science Publishers. pp. 211-233

Hepatic oxidative stress and apoptosis following acute alcohol
Everitt, H.E., Tewfik, I., Preedy, V.R. and Patel, V. 2009. Hepatic oxidative stress and apoptosis following acute alcohol. Alcohol & Alcoholism. 44, p. p85.

Nutrition and alcoholic liver disease
Everitt, H.E., Patel, V. and Tewfik, I. 2007. Nutrition and alcoholic liver disease. Nutrition Bulletin. 32 (2), pp. 138-144. https://doi.org/10.1111/j.1467-3010.2007.00627.x

Permalink - https://westminsterresearch.westminster.ac.uk/item/905vx/the-effect-of-acute-alcohol-exposure-on-hepatic-oxidative-stress-and-function-prevention-by-micronutrients


Restricted files

File

Under embargo indefinitely terms available at: http://rioxx.net/licenses/all-rights-reserved/

Share this

Usage statistics

98 total views
0 total downloads
These values cover views and downloads from WestminsterResearch and are for the period from September 2nd 2018, when this repository was created.