Author/Authors :
CieVlak, Anna Laboratory of Molecular Pharmacology - CHU de Quebec Research Centre and the Faculty of Pharmacy, Laval University, Quebec, Canada , Trottier, Jocelyn Laboratory of Molecular Pharmacology - CHU de Quebec Research Centre and the Faculty of Pharmacy, Laval University, Quebec, Canada , Verreault, Mélanie Laboratory of Molecular Pharmacology - CHU de Quebec Research Centre and the Faculty of Pharmacy, Laval University, Quebec, Canada , Milkiewicz, Piotr Liver and Internal Medicine - Medical University of Warsaw, Poland , Vohl, Marie-Claude Institute of Nutrition and Functional Foods (INAF) and CHU de Quebec Research Centre, Laval University, Qu ´ ebec, QC, Canada ´ , Barbier, Olivier Laboratory of Molecular Pharmacology - CHU de Quebec Research Centre and the Faculty of Pharmacy, Laval University, Quebec, Canada
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.
