Cargando…

Association of Hypomagnesemia and Liver Injury, Role of Gut-Barrier Dysfunction and Inflammation: Efficacy of Abstinence, and 2-Week Medical Management in Alcohol Use Disorder Patients

(1) We investigated the involvement of serum magnesium level in early alcoholic liver disease (ALD), gut barrier dysfunction, and inflammation in alcohol use disorder (AUD) patients; and lastly, the efficacy of 2-week abstinence and medical management to alleviate hypomagnesemia. (2) Forty-eight hea...

Descripción completa

Detalles Bibliográficos
Autores principales: Winrich, Evan J., Gala, Khushboo S., Rajhans, Abhas, Rios-Perez, Christian D., Royer, Amor J., Zamani, Zarlakhta, Parthasarathy, Ranganathan, Marsano-Obando, Luis S., Barve, Ashutosh J., Schwandt, Melanie L., Vatsalya, Vatsalya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569745/
https://www.ncbi.nlm.nih.gov/pubmed/36232646
http://dx.doi.org/10.3390/ijms231911332
_version_ 1784809931035115520
author Winrich, Evan J.
Gala, Khushboo S.
Rajhans, Abhas
Rios-Perez, Christian D.
Royer, Amor J.
Zamani, Zarlakhta
Parthasarathy, Ranganathan
Marsano-Obando, Luis S.
Barve, Ashutosh J.
Schwandt, Melanie L.
Vatsalya, Vatsalya
author_facet Winrich, Evan J.
Gala, Khushboo S.
Rajhans, Abhas
Rios-Perez, Christian D.
Royer, Amor J.
Zamani, Zarlakhta
Parthasarathy, Ranganathan
Marsano-Obando, Luis S.
Barve, Ashutosh J.
Schwandt, Melanie L.
Vatsalya, Vatsalya
author_sort Winrich, Evan J.
collection PubMed
description (1) We investigated the involvement of serum magnesium level in early alcoholic liver disease (ALD), gut barrier dysfunction, and inflammation in alcohol use disorder (AUD) patients; and lastly, the efficacy of 2-week abstinence and medical management to alleviate hypomagnesemia. (2) Forty-eight heavy drinking AUD patients (34 males (M)/14 females (F)) participated in this study. Patients were grouped by serum alanine aminotransferase (ALT) level (a marker of liver injury) as group 1 (Group 1 (Gr.1); ALT ≤ 40 U/L, 7M/8F, without any indication of early-stage ALD) and group 2 (Group 2 (Gr.2); ALT > 40 U/L, 27M/6F or early-stage ALD). These patients were sub-divided within each group into patients with normal magnesium (0.85 and more mmol/L) and deficient magnesium (less than 0.85 mmol/L) levels. All participants were assessed at baseline (BL) and received standard medical management for 2 weeks with reassessment at the treatment end (2w). (3) Female participants of this study showed a significantly lower baseline level of magnesium than their male counterparts. Gr.2 patients showed a greater propensity in the necrotic type of liver cell death, who reported higher chronic and recent heavy drinking. Magnesium level improved to the normal range in Gr.2 post-treatment, especially in the hypomagnesemia sub-group (0.77 ± 0.06 mmol/L (BL) vs. 0.85 ± 0.05 mmol/L (2w), p = 0.02). In Gr.2, both apoptotic (K18M30) and necrotic (K18M65) responses were significantly and independently associated with inflammasome activity comprising of LBP (Lipopolysaccharide binding-protein) and TNFα (Tumor necrosis factor -α), along with serum magnesium. (4) In AUD patients with liver injury, 2-week medical management seems to improve magnesium to a normal level. This group exhibited inflammatory activity (LBP and TNFα) contributing to clinically significant hypomagnesemia. In this group, the level of magnesium, along with the unique inflammatory activity, seems to significantly predict apoptotic and necrotic types of hepatocyte death.
format Online
Article
Text
id pubmed-9569745
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-95697452022-10-17 Association of Hypomagnesemia and Liver Injury, Role of Gut-Barrier Dysfunction and Inflammation: Efficacy of Abstinence, and 2-Week Medical Management in Alcohol Use Disorder Patients Winrich, Evan J. Gala, Khushboo S. Rajhans, Abhas Rios-Perez, Christian D. Royer, Amor J. Zamani, Zarlakhta Parthasarathy, Ranganathan Marsano-Obando, Luis S. Barve, Ashutosh J. Schwandt, Melanie L. Vatsalya, Vatsalya Int J Mol Sci Article (1) We investigated the involvement of serum magnesium level in early alcoholic liver disease (ALD), gut barrier dysfunction, and inflammation in alcohol use disorder (AUD) patients; and lastly, the efficacy of 2-week abstinence and medical management to alleviate hypomagnesemia. (2) Forty-eight heavy drinking AUD patients (34 males (M)/14 females (F)) participated in this study. Patients were grouped by serum alanine aminotransferase (ALT) level (a marker of liver injury) as group 1 (Group 1 (Gr.1); ALT ≤ 40 U/L, 7M/8F, without any indication of early-stage ALD) and group 2 (Group 2 (Gr.2); ALT > 40 U/L, 27M/6F or early-stage ALD). These patients were sub-divided within each group into patients with normal magnesium (0.85 and more mmol/L) and deficient magnesium (less than 0.85 mmol/L) levels. All participants were assessed at baseline (BL) and received standard medical management for 2 weeks with reassessment at the treatment end (2w). (3) Female participants of this study showed a significantly lower baseline level of magnesium than their male counterparts. Gr.2 patients showed a greater propensity in the necrotic type of liver cell death, who reported higher chronic and recent heavy drinking. Magnesium level improved to the normal range in Gr.2 post-treatment, especially in the hypomagnesemia sub-group (0.77 ± 0.06 mmol/L (BL) vs. 0.85 ± 0.05 mmol/L (2w), p = 0.02). In Gr.2, both apoptotic (K18M30) and necrotic (K18M65) responses were significantly and independently associated with inflammasome activity comprising of LBP (Lipopolysaccharide binding-protein) and TNFα (Tumor necrosis factor -α), along with serum magnesium. (4) In AUD patients with liver injury, 2-week medical management seems to improve magnesium to a normal level. This group exhibited inflammatory activity (LBP and TNFα) contributing to clinically significant hypomagnesemia. In this group, the level of magnesium, along with the unique inflammatory activity, seems to significantly predict apoptotic and necrotic types of hepatocyte death. MDPI 2022-09-26 /pmc/articles/PMC9569745/ /pubmed/36232646 http://dx.doi.org/10.3390/ijms231911332 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Winrich, Evan J.
Gala, Khushboo S.
Rajhans, Abhas
Rios-Perez, Christian D.
Royer, Amor J.
Zamani, Zarlakhta
Parthasarathy, Ranganathan
Marsano-Obando, Luis S.
Barve, Ashutosh J.
Schwandt, Melanie L.
Vatsalya, Vatsalya
Association of Hypomagnesemia and Liver Injury, Role of Gut-Barrier Dysfunction and Inflammation: Efficacy of Abstinence, and 2-Week Medical Management in Alcohol Use Disorder Patients
title Association of Hypomagnesemia and Liver Injury, Role of Gut-Barrier Dysfunction and Inflammation: Efficacy of Abstinence, and 2-Week Medical Management in Alcohol Use Disorder Patients
title_full Association of Hypomagnesemia and Liver Injury, Role of Gut-Barrier Dysfunction and Inflammation: Efficacy of Abstinence, and 2-Week Medical Management in Alcohol Use Disorder Patients
title_fullStr Association of Hypomagnesemia and Liver Injury, Role of Gut-Barrier Dysfunction and Inflammation: Efficacy of Abstinence, and 2-Week Medical Management in Alcohol Use Disorder Patients
title_full_unstemmed Association of Hypomagnesemia and Liver Injury, Role of Gut-Barrier Dysfunction and Inflammation: Efficacy of Abstinence, and 2-Week Medical Management in Alcohol Use Disorder Patients
title_short Association of Hypomagnesemia and Liver Injury, Role of Gut-Barrier Dysfunction and Inflammation: Efficacy of Abstinence, and 2-Week Medical Management in Alcohol Use Disorder Patients
title_sort association of hypomagnesemia and liver injury, role of gut-barrier dysfunction and inflammation: efficacy of abstinence, and 2-week medical management in alcohol use disorder patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569745/
https://www.ncbi.nlm.nih.gov/pubmed/36232646
http://dx.doi.org/10.3390/ijms231911332
work_keys_str_mv AT winrichevanj associationofhypomagnesemiaandliverinjuryroleofgutbarrierdysfunctionandinflammationefficacyofabstinenceand2weekmedicalmanagementinalcoholusedisorderpatients
AT galakhushboos associationofhypomagnesemiaandliverinjuryroleofgutbarrierdysfunctionandinflammationefficacyofabstinenceand2weekmedicalmanagementinalcoholusedisorderpatients
AT rajhansabhas associationofhypomagnesemiaandliverinjuryroleofgutbarrierdysfunctionandinflammationefficacyofabstinenceand2weekmedicalmanagementinalcoholusedisorderpatients
AT riosperezchristiand associationofhypomagnesemiaandliverinjuryroleofgutbarrierdysfunctionandinflammationefficacyofabstinenceand2weekmedicalmanagementinalcoholusedisorderpatients
AT royeramorj associationofhypomagnesemiaandliverinjuryroleofgutbarrierdysfunctionandinflammationefficacyofabstinenceand2weekmedicalmanagementinalcoholusedisorderpatients
AT zamanizarlakhta associationofhypomagnesemiaandliverinjuryroleofgutbarrierdysfunctionandinflammationefficacyofabstinenceand2weekmedicalmanagementinalcoholusedisorderpatients
AT parthasarathyranganathan associationofhypomagnesemiaandliverinjuryroleofgutbarrierdysfunctionandinflammationefficacyofabstinenceand2weekmedicalmanagementinalcoholusedisorderpatients
AT marsanoobandoluiss associationofhypomagnesemiaandliverinjuryroleofgutbarrierdysfunctionandinflammationefficacyofabstinenceand2weekmedicalmanagementinalcoholusedisorderpatients
AT barveashutoshj associationofhypomagnesemiaandliverinjuryroleofgutbarrierdysfunctionandinflammationefficacyofabstinenceand2weekmedicalmanagementinalcoholusedisorderpatients
AT schwandtmelaniel associationofhypomagnesemiaandliverinjuryroleofgutbarrierdysfunctionandinflammationefficacyofabstinenceand2weekmedicalmanagementinalcoholusedisorderpatients
AT vatsalyavatsalya associationofhypomagnesemiaandliverinjuryroleofgutbarrierdysfunctionandinflammationefficacyofabstinenceand2weekmedicalmanagementinalcoholusedisorderpatients