N-3 Polyunsaturated Fatty Acids Stimulate Bile Acid Detoxification in Human Cell Models.
Can J Gastroenterol Hepatol
; 2018: 6031074, 2018.
Article
em En
| MEDLINE
| ID: mdl-29850457
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos e Sais Biliares
/
Expressão Gênica
/
Ácido Eicosapentaenoico
/
Ácidos Docosa-Hexaenoicos
Limite:
Humans
Idioma:
En
Revista:
Can J Gastroenterol Hepatol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Canadá