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The Effect of Phenolic Compounds on the Transport of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine in Caco‐2 Cell Monolayers
Author(s) -
Hong Yun-Jin,
Nam Mi-Hyun,
Oh Ji-Sun,
Oh Jun-Gu,
Lee Kwang-Won
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.988.6
Subject(s) - caffeic acid , chemistry , efflux , multidrug resistance associated protein 2 , caco 2 , biochemistry , enterocyte , viability assay , metabolite , cell , transporter , small intestine , atp binding cassette transporter , gene , antioxidant
The goal of this study was to investigate the effect of caffeic acid on the transport of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) in Caco‐2 cell monolayer and the expression of individual efflux transporters. PhIP is formed as a by‐product of Maillard reaction during cooking or frying of protein‐rich foods at high temperatures. PhIP is metabolized in the liver by cytochromes P450 1A1 and 1A2 to its carcinogenic metabolite N‐hydroxy PhIP. The ABC transporters are capable of transporting the food‐borne procarcinogen PhIP back to the intestinal lumen. P‐gp, MRP2 and BCRP in the apical membrane of the enterocyte are involved in the efflux of compounds from the enterocytes. In the present study, MTT assay was performed to confirm the cell viability was not affected by sample concentration and incubation period. The uptake and efflux of PhIP was assessed by determining bidirectional apparent permeability coefficients. Results showed that the uptake of PhIP was reduced in the presence of caffeic acid. The efflux ratio of PhIP in the presence of caffeic acid was also significantly decreased, compared with control (p<0.05). Caco‐2 cells exposed to caffeic acid for 3h also exhibited higher mRNA levels of P‐glycoprotein, BCRP, and Multidrug Resistance Protein 2 than that of control (p<0.05). These results indicated that caffeic acid may reduce uptake and increase efflux of PhIP by up‐regulating efflux transporter mRNA levels.