Cargando…

Acute ethanol-induced liver injury is prevented by betaine administration

Binge drinking is the most common form of excessive alcohol use. Repeated episodes of binge drinking cause multiple organ injuries, including liver damage. We previously demonstrated that chronic ethanol administration causes a decline in the intrahepatic ratio of S-adenosylmethionine (SAM) to S-ade...

Descripción completa

Detalles Bibliográficos
Autores principales: Arumugam, Madan Kumar, Chava, Srinivas, Perumal, Sathish Kumar, Paal, Matthew C., Rasineni, Karuna, Ganesan, Murali, Donohue, Terrence M., Osna, Natalia A., Kharbanda, Kusum K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577233/
https://www.ncbi.nlm.nih.gov/pubmed/36267591
http://dx.doi.org/10.3389/fphys.2022.940148
_version_ 1784811713860730880
author Arumugam, Madan Kumar
Chava, Srinivas
Perumal, Sathish Kumar
Paal, Matthew C.
Rasineni, Karuna
Ganesan, Murali
Donohue, Terrence M.
Osna, Natalia A.
Kharbanda, Kusum K.
author_facet Arumugam, Madan Kumar
Chava, Srinivas
Perumal, Sathish Kumar
Paal, Matthew C.
Rasineni, Karuna
Ganesan, Murali
Donohue, Terrence M.
Osna, Natalia A.
Kharbanda, Kusum K.
author_sort Arumugam, Madan Kumar
collection PubMed
description Binge drinking is the most common form of excessive alcohol use. Repeated episodes of binge drinking cause multiple organ injuries, including liver damage. We previously demonstrated that chronic ethanol administration causes a decline in the intrahepatic ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). This decline causes impairments in essential methylation reactions that result in alcohol-induced fatty liver (steatosis) and other features of alcohol-associated liver disease (ALD). Co-treatment with betaine during chronic ethanol feeding, normalizes hepatocellular SAM:SAH ratio and alleviates many features of liver damage including steatosis. Here, we sought to examine whether betaine treatment similarly protects against liver injury in an alcohol binge-drinking model. We hypothesized that ethanol binge with prior or simultaneous betaine administration would prevent or attenuate acute alcohol-induced liver damage. Male C57Bl/6 mice were gavaged twice, 12 h apart, with either 6 g ethanol/kg BW or with an equal volume/kg BW of 0.9% NaCl. Two separate groups of mice (n = 5/group) were gavaged with 4 g betaine/kg BW, either 2 h before or simultaneously with the ethanol or saline gavages. All mice were sacrificed 8 h after the last gavage and serum and liver parameters were quantified. Ethanol binges caused a 50% decrease in hepatic SAM:SAH ratio and a >3-fold rise in liver triglycerides (p ≤ 0.05). These latter changes were accompanied by elevated serum AST and ALT activities and blood alcohol concentrations (BAC) that were ∼three-times higher than the legal limit of intoxication in humans. Mice that were treated with betaine 2 h before or simultaneously with the ethanol binges exhibited similar BAC as in mice given ethanol-alone. Both betaine treatments significantly elevated hepatic SAM levels thereby normalizing the SAM:SAH ratio and attenuating hepatic steatosis and other injury parameters, compared with mice given ethanol alone. Simultaneous betaine co-administration with ethanol was more effective in preventing or attenuating liver injury than betaine given before ethanol gavage. Our findings confirm the potential therapeutic value of betaine administration in preventing liver injury after binge drinking in an animal model.
format Online
Article
Text
id pubmed-9577233
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-95772332022-10-19 Acute ethanol-induced liver injury is prevented by betaine administration Arumugam, Madan Kumar Chava, Srinivas Perumal, Sathish Kumar Paal, Matthew C. Rasineni, Karuna Ganesan, Murali Donohue, Terrence M. Osna, Natalia A. Kharbanda, Kusum K. Front Physiol Physiology Binge drinking is the most common form of excessive alcohol use. Repeated episodes of binge drinking cause multiple organ injuries, including liver damage. We previously demonstrated that chronic ethanol administration causes a decline in the intrahepatic ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). This decline causes impairments in essential methylation reactions that result in alcohol-induced fatty liver (steatosis) and other features of alcohol-associated liver disease (ALD). Co-treatment with betaine during chronic ethanol feeding, normalizes hepatocellular SAM:SAH ratio and alleviates many features of liver damage including steatosis. Here, we sought to examine whether betaine treatment similarly protects against liver injury in an alcohol binge-drinking model. We hypothesized that ethanol binge with prior or simultaneous betaine administration would prevent or attenuate acute alcohol-induced liver damage. Male C57Bl/6 mice were gavaged twice, 12 h apart, with either 6 g ethanol/kg BW or with an equal volume/kg BW of 0.9% NaCl. Two separate groups of mice (n = 5/group) were gavaged with 4 g betaine/kg BW, either 2 h before or simultaneously with the ethanol or saline gavages. All mice were sacrificed 8 h after the last gavage and serum and liver parameters were quantified. Ethanol binges caused a 50% decrease in hepatic SAM:SAH ratio and a >3-fold rise in liver triglycerides (p ≤ 0.05). These latter changes were accompanied by elevated serum AST and ALT activities and blood alcohol concentrations (BAC) that were ∼three-times higher than the legal limit of intoxication in humans. Mice that were treated with betaine 2 h before or simultaneously with the ethanol binges exhibited similar BAC as in mice given ethanol-alone. Both betaine treatments significantly elevated hepatic SAM levels thereby normalizing the SAM:SAH ratio and attenuating hepatic steatosis and other injury parameters, compared with mice given ethanol alone. Simultaneous betaine co-administration with ethanol was more effective in preventing or attenuating liver injury than betaine given before ethanol gavage. Our findings confirm the potential therapeutic value of betaine administration in preventing liver injury after binge drinking in an animal model. Frontiers Media S.A. 2022-10-04 /pmc/articles/PMC9577233/ /pubmed/36267591 http://dx.doi.org/10.3389/fphys.2022.940148 Text en Copyright © 2022 Arumugam, Chava, Perumal, Paal, Rasineni, Ganesan, Donohue, Osna and Kharbanda. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Arumugam, Madan Kumar
Chava, Srinivas
Perumal, Sathish Kumar
Paal, Matthew C.
Rasineni, Karuna
Ganesan, Murali
Donohue, Terrence M.
Osna, Natalia A.
Kharbanda, Kusum K.
Acute ethanol-induced liver injury is prevented by betaine administration
title Acute ethanol-induced liver injury is prevented by betaine administration
title_full Acute ethanol-induced liver injury is prevented by betaine administration
title_fullStr Acute ethanol-induced liver injury is prevented by betaine administration
title_full_unstemmed Acute ethanol-induced liver injury is prevented by betaine administration
title_short Acute ethanol-induced liver injury is prevented by betaine administration
title_sort acute ethanol-induced liver injury is prevented by betaine administration
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577233/
https://www.ncbi.nlm.nih.gov/pubmed/36267591
http://dx.doi.org/10.3389/fphys.2022.940148
work_keys_str_mv AT arumugammadankumar acuteethanolinducedliverinjuryispreventedbybetaineadministration
AT chavasrinivas acuteethanolinducedliverinjuryispreventedbybetaineadministration
AT perumalsathishkumar acuteethanolinducedliverinjuryispreventedbybetaineadministration
AT paalmatthewc acuteethanolinducedliverinjuryispreventedbybetaineadministration
AT rasinenikaruna acuteethanolinducedliverinjuryispreventedbybetaineadministration
AT ganesanmurali acuteethanolinducedliverinjuryispreventedbybetaineadministration
AT donohueterrencem acuteethanolinducedliverinjuryispreventedbybetaineadministration
AT osnanataliaa acuteethanolinducedliverinjuryispreventedbybetaineadministration
AT kharbandakusumk acuteethanolinducedliverinjuryispreventedbybetaineadministration