curcumin and perfluorooctanoic-acid

Oral ingestion is considered an important route of human exposure to perfluorooctanoic acid (PFOA) and its alternative hexafluoropropylene oxide trimer acid (HFPO-TA). Bioactive compounds are widely used as dietary supplements and food additives. However, little is known about the influence of dietary bioactive compounds on the bioavailability of PFOA and HFPO-TA. Here, three dietary bioactive compounds, β-carotene, quercetin and curcumin, were selected to study their influence on the relative bioavailability (RBA) of PFOA and HFPO-TA in soil using a mouse model. Compared to the control group (68.7 ± 6.27 %), quercetin and curcumin at medium and high doses (20 and 100 mg/kg/d) significantly (p < 0.05) decreased PFOA RBA to 55.2 ± 4.85-56.4 ± 4.57 % and 48.3 ± 5.49-48.6 ± 5.44 %, respectively. Mechanism study showed that medium- and high-dose quercetin as well as high-dose curcumin increased urinary excretion of PFOA by 33.6-35.6 % and 32.2 % through upregulating renal expression of multidrug resistance protein 2 (Mrp2) (1.52-1.63 folds) and Mrp4 (1.26-1.53 folds), thereby reducing PFOA accumulation. In PFOA-treated groups, quercetin at medium and high doses dramatically downregulated the hepatic expression of organic anion transport polypeptides (Oatp1a6, Oatp1b2), organic anion transport proteins (Oat1, Oat2), and fatty acid binding proteins (FABP4, FABP12), while curcumin at medium and high doses inhibited the hepatic expression of Oatp1a6, Oat1 and Oat2. These downregulated genes may reduce the transport of PFOA from blood to liver, and in turn decrease the PFOA RBA. However, β-carotene, quercetin and curcumin exhibited no significant effect on RBA and excretion of HFPO-TA (p > 0.05). This indicated the different absorption mechanisms between PFOA and HFPO-TA, and further research is warranted. This study provided a novel perspective for establishing environmentally friendly ways to reduce health hazards from per- and polyfluoroalkyl substances (PFASs).

Topics: beta Carotene; Biological Availability; Curcumin; Fatty Acid-Binding Proteins; Fluorocarbons; Humans; Quercetin

Altered gap junctional intercellular communication (GJIC) has been associated with chemical carcinogenesis, where both chemical tumor promoters and chemopreventive agents (CPAs) are known to conversely modulate GJIC. The aim of this study was to investigate whether attenuation of chemically inhibited GJIC represents a common outcome induced by different CPAs, which could be effectively evaluated using in vitro methods. Rat liver epithelial cells WB-F344 were pretreated with a CPA for either 30 min or 24 h, and then exposed to GJIC-inhibiting concentration of a selected tumor promoter or environmental toxicant [12-O-tetradecanoylphorbol-13-acetate (TPA), lindane, fluoranthene, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), perfluorooctanoic acid (PFOA), or pentachlorophenol]. Out of nine CPAs tested, quercetin and silibinin elicited the most pronounced effects, preventing the dysregulation of GJIC by all the GJIC inhibitors, but DDT. Metformin and curcumin attenuated the effects of three GJIC inhibitors, whereas the other CPAs prevented the effects of two (diallyl sulfide, emodin) or one (indole-3-carbinol, thymoquinone) GJIC inhibitor. Significant attenuation of chemically induced inhibition of GJIC was observed in 27 (50%) out of 54 possible combinations of nine CPAs and six GJIC inhibitors. Our data demonstrate that in vitro evaluation of GJIC can be used as an effective screening tool for identification of chemicals with potential chemopreventive activity.

Topics: Animals; Anticarcinogenic Agents; Caprylates; Carcinogens; Cell Communication; Cell Survival; Cells, Cultured; Curcumin; DDT; Epithelial Cells; Fluorenes; Fluorocarbons; Gap Junctions; Hexachlorocyclohexane; Liver; Metformin; Rats; Rats, Inbred F344; Tetradecanoylphorbol Acetate