Cargando…
Omega-3 Polyunsaturated Fatty Acid: A Pharmaco-Nutraceutical Approach to Improve the Responsiveness to Ursodeoxycholic Acid
Ursodeoxycholic acid (UDCA) is the first line therapy for the treatment of cholestatic and autoimmune liver diseases. Its clinical use is currently limited by a significant proportion of non-responder patients. Polyunsaturated fatty acids (n-3 PUFAs) possess important anti-inflammatory properties an...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400581/ https://www.ncbi.nlm.nih.gov/pubmed/34444777 http://dx.doi.org/10.3390/nu13082617 |
_version_ | 1783745348635721728 |
---|---|
author | Thérien, Ariane Cieślak, Anna Verreault, Mélanie Perreault, Martin Trottier, Jocelyn Gobeil, Stéphane Vohl, Marie-Claude Barbier, Olivier |
author_facet | Thérien, Ariane Cieślak, Anna Verreault, Mélanie Perreault, Martin Trottier, Jocelyn Gobeil, Stéphane Vohl, Marie-Claude Barbier, Olivier |
author_sort | Thérien, Ariane |
collection | PubMed |
description | Ursodeoxycholic acid (UDCA) is the first line therapy for the treatment of cholestatic and autoimmune liver diseases. Its clinical use is currently limited by a significant proportion of non-responder patients. Polyunsaturated fatty acids (n-3 PUFAs) possess important anti-inflammatory properties and protect liver cells against bile acid (BA)-induced toxicity. The present study was designed to rapidly evaluate whether combining n-3 PUFAs (i.e., eicosapentaenoic [EPA] and docosahexaenoic [DHA] acids) to UDCA would provide additional benefits when compared to the drug alone. The parameters evaluated were (i) the expression of genes governing BA synthesis, transport, and metabolism; (ii) the prevention of BA-induced apoptosis and endoplasmic reticulum (ER)-stress; and (iii) the control of BA- and LPS-dependent inflammation. In the absence of n-3 PUFAs, most of the parameters investigated were unaffected by UDCA or were only altered by the higher dose (500 µM) of the drug. By contrast, in the presence of EPA/DHA (50/50 µM), all parameters showed a strongly improved response and the lowest UDCA dosage (50 µM) provided equal or better benefits than the highest dose used alone. For example, the combination EPA/DHA + UDCA 50 µM caused comparable down-regulation of the CYP7A1 gene expression and of the BA-induced caspase 3 activity as observed with UDCA 500 µM. In conclusion, these results suggest that the addition of n-3 PUFAs to UDCA may improve the response to the drug, and that such a pharmaco-nutraceutical approach could be used in clinic to open the narrow therapeutic dose of UDCA in cholestatic liver diseases. |
format | Online Article Text |
id | pubmed-8400581 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84005812021-08-29 Omega-3 Polyunsaturated Fatty Acid: A Pharmaco-Nutraceutical Approach to Improve the Responsiveness to Ursodeoxycholic Acid Thérien, Ariane Cieślak, Anna Verreault, Mélanie Perreault, Martin Trottier, Jocelyn Gobeil, Stéphane Vohl, Marie-Claude Barbier, Olivier Nutrients Article Ursodeoxycholic acid (UDCA) is the first line therapy for the treatment of cholestatic and autoimmune liver diseases. Its clinical use is currently limited by a significant proportion of non-responder patients. Polyunsaturated fatty acids (n-3 PUFAs) possess important anti-inflammatory properties and protect liver cells against bile acid (BA)-induced toxicity. The present study was designed to rapidly evaluate whether combining n-3 PUFAs (i.e., eicosapentaenoic [EPA] and docosahexaenoic [DHA] acids) to UDCA would provide additional benefits when compared to the drug alone. The parameters evaluated were (i) the expression of genes governing BA synthesis, transport, and metabolism; (ii) the prevention of BA-induced apoptosis and endoplasmic reticulum (ER)-stress; and (iii) the control of BA- and LPS-dependent inflammation. In the absence of n-3 PUFAs, most of the parameters investigated were unaffected by UDCA or were only altered by the higher dose (500 µM) of the drug. By contrast, in the presence of EPA/DHA (50/50 µM), all parameters showed a strongly improved response and the lowest UDCA dosage (50 µM) provided equal or better benefits than the highest dose used alone. For example, the combination EPA/DHA + UDCA 50 µM caused comparable down-regulation of the CYP7A1 gene expression and of the BA-induced caspase 3 activity as observed with UDCA 500 µM. In conclusion, these results suggest that the addition of n-3 PUFAs to UDCA may improve the response to the drug, and that such a pharmaco-nutraceutical approach could be used in clinic to open the narrow therapeutic dose of UDCA in cholestatic liver diseases. MDPI 2021-07-29 /pmc/articles/PMC8400581/ /pubmed/34444777 http://dx.doi.org/10.3390/nu13082617 Text en © 2021 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 Thérien, Ariane Cieślak, Anna Verreault, Mélanie Perreault, Martin Trottier, Jocelyn Gobeil, Stéphane Vohl, Marie-Claude Barbier, Olivier Omega-3 Polyunsaturated Fatty Acid: A Pharmaco-Nutraceutical Approach to Improve the Responsiveness to Ursodeoxycholic Acid |
title | Omega-3 Polyunsaturated Fatty Acid: A Pharmaco-Nutraceutical Approach to Improve the Responsiveness to Ursodeoxycholic Acid |
title_full | Omega-3 Polyunsaturated Fatty Acid: A Pharmaco-Nutraceutical Approach to Improve the Responsiveness to Ursodeoxycholic Acid |
title_fullStr | Omega-3 Polyunsaturated Fatty Acid: A Pharmaco-Nutraceutical Approach to Improve the Responsiveness to Ursodeoxycholic Acid |
title_full_unstemmed | Omega-3 Polyunsaturated Fatty Acid: A Pharmaco-Nutraceutical Approach to Improve the Responsiveness to Ursodeoxycholic Acid |
title_short | Omega-3 Polyunsaturated Fatty Acid: A Pharmaco-Nutraceutical Approach to Improve the Responsiveness to Ursodeoxycholic Acid |
title_sort | omega-3 polyunsaturated fatty acid: a pharmaco-nutraceutical approach to improve the responsiveness to ursodeoxycholic acid |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400581/ https://www.ncbi.nlm.nih.gov/pubmed/34444777 http://dx.doi.org/10.3390/nu13082617 |
work_keys_str_mv | AT therienariane omega3polyunsaturatedfattyacidapharmaconutraceuticalapproachtoimprovetheresponsivenesstoursodeoxycholicacid AT cieslakanna omega3polyunsaturatedfattyacidapharmaconutraceuticalapproachtoimprovetheresponsivenesstoursodeoxycholicacid AT verreaultmelanie omega3polyunsaturatedfattyacidapharmaconutraceuticalapproachtoimprovetheresponsivenesstoursodeoxycholicacid AT perreaultmartin omega3polyunsaturatedfattyacidapharmaconutraceuticalapproachtoimprovetheresponsivenesstoursodeoxycholicacid AT trottierjocelyn omega3polyunsaturatedfattyacidapharmaconutraceuticalapproachtoimprovetheresponsivenesstoursodeoxycholicacid AT gobeilstephane omega3polyunsaturatedfattyacidapharmaconutraceuticalapproachtoimprovetheresponsivenesstoursodeoxycholicacid AT vohlmarieclaude omega3polyunsaturatedfattyacidapharmaconutraceuticalapproachtoimprovetheresponsivenesstoursodeoxycholicacid AT barbierolivier omega3polyunsaturatedfattyacidapharmaconutraceuticalapproachtoimprovetheresponsivenesstoursodeoxycholicacid |