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Anti‐oxidant and Anti‐inflammatory Activity of Tocopherol Isomers Modulates the Nrf‐2 and NfκB Activation in Caco‐2 Human Intestinal Cell Line
Author(s) -
elisia ingrid,
Kitts David
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.823.7
Subject(s) - oxygen radical absorbance capacity , chemistry , antioxidant , caco 2 , oxidative stress , biochemistry , interleukin 8 , reactive oxygen species , inflammation , cell , dpph , biology , immunology
The objective of this study was to determine if the antioxidant activity of tocopherol (Toc) isomers translated to a protection against inflammation through oxidative‐stress related pathways in the Caco‐2 intestinal cell line. Antioxidant activities of major Toc isomers, determined using Oxygen Radical Absorbance Capacity (ORAC) chemical assay, followed a relative order of δToc>γToc>αToc. The anti‐inflammatory activity of Toc isomers was determined using interferon γ/phorbol myristate acetate (IFNγ/PMA) cocktail to stimulate interleukin 8 (IL8) secretion from Caco‐2 cells. Both αToc and γToc concentration‐dependently suppressed IL8 production from IFNγ/PMA‐stimulated cells. Delta Toc on the other hand was more effective at a lower concentration to modulate IL8 production compared to αToc and γToc, while being the least effective high concentration. Exposure of Caco‐2 cells to IFNγ/PMA activated both stress‐responsive NfκB pro‐inflammatory and Nrf2 antioxidant enzyme pathways. Only αToc concentration‐dependently suppressed NfκB activation induced by IFNγ/PMA cocktail. There was also an isomer‐dependent difference in the NfκB modulating activity, with αToc being the greatest followed by γToc and δToc (P<0.05). On the other hand, δToc was shown to further promote Nrf2 nuclear translocation, while αToc had no effect. To conclude, the antioxidative pattern exhibited by Toc isomers does not correspond to the anti‐inflammatory activity in Caco‐2 cells; a finding that is attributed to either a non‐antioxidant function of Toc isomers, or the formation of pro‐oxidants at high concentrations of Tocs. Grant Funding Source : UBC‐FNH vitamin research fund and NSERC