N-3 Polyunsaturated Fatty Acids Stimulate Bile Acid Detoxification in Human Cell Models
Cholestasis is characterized by the accumulation of toxic bile acids (BAs) in liver cells. The present study aimed to evaluate the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), such as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, on BA homeostasis and toxicity in human cell mode...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Canadian Journal of Gastroenterology and Hepatology |
| Online Access: | http://dx.doi.org/10.1155/2018/6031074 |
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| author | Anna Cieślak Jocelyn Trottier Mélanie Verreault Piotr Milkiewicz Marie-Claude Vohl Olivier Barbier |
| author_facet | Anna Cieślak Jocelyn Trottier Mélanie Verreault Piotr Milkiewicz Marie-Claude Vohl Olivier Barbier |
| author_sort | Anna Cieślak |
| collection | DOAJ |
| description | Cholestasis is characterized by the accumulation of toxic bile acids (BAs) in liver cells. The present study aimed to evaluate the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), such as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, on BA homeostasis and toxicity in human cell models. The effects of EPA and/or DHA on the expression of genes involved in the maintenance of BA homeostasis were analyzed in human hepatoma (HepG2) and colon carcinoma (Caco-2) cells, as well as in primary culture of human intestinal (InEpC) and renal (RPTEC) cells. Extracellular BA species were quantified in culture media using LC-MS/MS. BA-induced toxicity was evaluated using caspase-3 and flow cytometry assays. Gene expression analyses of HepG2 cells reveal that n-3 PUFAs reduce the expression of genes involved in BA synthesis (CYP7A1, CYP27A1) and uptake (NTCP), while activating genes encoding metabolic enzymes (SULT2A1) and excretion transporters (MRP2, MRP3). N-3 PUFAs also generate a less toxic BA pool and prevent the BA-dependent activation of apoptosis in HepG2 cells. Conclusion. The present study reveals that n-3 PUFAs stimulate BA detoxification. |
| format | Article |
| id | doaj-art-33100f0ee5ab433999b158f45fe3d37a |
| institution | Kabale University |
| issn | 2291-2789 2291-2797 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Canadian Journal of Gastroenterology and Hepatology |
| spelling | doaj-art-33100f0ee5ab433999b158f45fe3d37a2025-02-03T01:31:24ZengWileyCanadian Journal of Gastroenterology and Hepatology2291-27892291-27972018-01-01201810.1155/2018/60310746031074N-3 Polyunsaturated Fatty Acids Stimulate Bile Acid Detoxification in Human Cell ModelsAnna Cieślak0Jocelyn Trottier1Mélanie Verreault2Piotr Milkiewicz3Marie-Claude Vohl4Olivier Barbier5Laboratory of Molecular Pharmacology, CHU de Québec Research Centre and the Faculty of Pharmacy, Laval University, Québec, QC, CanadaLaboratory of Molecular Pharmacology, CHU de Québec Research Centre and the Faculty of Pharmacy, Laval University, Québec, QC, CanadaLaboratory of Molecular Pharmacology, CHU de Québec Research Centre and the Faculty of Pharmacy, Laval University, Québec, QC, CanadaLiver and Internal Medicine, Medical University of Warsaw, Warsaw, PolandInstitute of Nutrition and Functional Foods (INAF) and CHU de Québec Research Centre, Laval University, Québec, QC, CanadaLaboratory of Molecular Pharmacology, CHU de Québec Research Centre and the Faculty of Pharmacy, Laval University, Québec, QC, CanadaCholestasis is characterized by the accumulation of toxic bile acids (BAs) in liver cells. The present study aimed to evaluate the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), such as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, on BA homeostasis and toxicity in human cell models. The effects of EPA and/or DHA on the expression of genes involved in the maintenance of BA homeostasis were analyzed in human hepatoma (HepG2) and colon carcinoma (Caco-2) cells, as well as in primary culture of human intestinal (InEpC) and renal (RPTEC) cells. Extracellular BA species were quantified in culture media using LC-MS/MS. BA-induced toxicity was evaluated using caspase-3 and flow cytometry assays. Gene expression analyses of HepG2 cells reveal that n-3 PUFAs reduce the expression of genes involved in BA synthesis (CYP7A1, CYP27A1) and uptake (NTCP), while activating genes encoding metabolic enzymes (SULT2A1) and excretion transporters (MRP2, MRP3). N-3 PUFAs also generate a less toxic BA pool and prevent the BA-dependent activation of apoptosis in HepG2 cells. Conclusion. The present study reveals that n-3 PUFAs stimulate BA detoxification.http://dx.doi.org/10.1155/2018/6031074 |
| spellingShingle | Anna Cieślak Jocelyn Trottier Mélanie Verreault Piotr Milkiewicz Marie-Claude Vohl Olivier Barbier N-3 Polyunsaturated Fatty Acids Stimulate Bile Acid Detoxification in Human Cell Models Canadian Journal of Gastroenterology and Hepatology |
| title | N-3 Polyunsaturated Fatty Acids Stimulate Bile Acid Detoxification in Human Cell Models |
| title_full | N-3 Polyunsaturated Fatty Acids Stimulate Bile Acid Detoxification in Human Cell Models |
| title_fullStr | N-3 Polyunsaturated Fatty Acids Stimulate Bile Acid Detoxification in Human Cell Models |
| title_full_unstemmed | N-3 Polyunsaturated Fatty Acids Stimulate Bile Acid Detoxification in Human Cell Models |
| title_short | N-3 Polyunsaturated Fatty Acids Stimulate Bile Acid Detoxification in Human Cell Models |
| title_sort | n 3 polyunsaturated fatty acids stimulate bile acid detoxification in human cell models |
| url | http://dx.doi.org/10.1155/2018/6031074 |
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