N-3 Polyunsaturated Fatty Acids Stimulate Bile Acid Detoxification in Human Cell Models. (5th April 2018)

• Record Type: Journal Article
• Authors: Cieślak, Anna; Trottier, Jocelyn; Verreault, Mélanie; Milkiewicz, Piotr; Vohl, Marie-Claude; Barbier, Olivier
• Other Names: Mauriz José L. Academic Editor.
• Is Part Of: Canadian journal of gastroenterology & hepatology. Volume 2018(2018)
• Publication Date: 2018-04-05
• Subjects: Digestive organs -- Diseases -- Periodicals; Gastroenterology -- Periodicals; Digestive organs -- Diseases; Gastroenterology; Canada; Digestive System Diseases -- Periodicals; Gastroenterology -- Periodicals; Periodicals; Electronic journals; Fulltext; Internet Resources; Periodicals; 616.3
• DOI: 10.1155/2018/6031074
• Languages: English
• ISSNs: 2291-2789

Abstract

Abstract : 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.