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Eicosapentaenoic acid prevents TCDD ‐induced oxidative stress and inflammatory response by modulating MAP kinases and redox‐sensitive transcription factors
Author(s) -
Palanisamy Kalaiselvi,
Krishnaswamy Rajashree,
Paramasivan Poornima,
ChihYang Huang,
Vishwanadha Vijaya Padma
Publication year - 2015
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13247
Subject(s) - oxidative stress , cytoprotection , chemistry , reactive oxygen species , p38 mitogen activated protein kinases , eicosapentaenoic acid , kinase , oxidative phosphorylation , microbiology and biotechnology , biochemistry , mapk/erk pathway , biology , pharmacology , fatty acid , polyunsaturated fatty acid
Background and Purpose Oxidative stress and subsequent activation of inflammatory responses is a widely accepted consequence of exposure to environmental toxins. TCDD (2,3,7,8‐tetrachlorodibenzo‐p‐dioxin), a well‐known environmental toxin, exerts its toxicity through many signalling mechanisms, with liver being the principal organ affected. However, an effective antidote to TCDD ‐induced toxicity is unknown. The present study evaluated the effect of eicosapentaenoic acid ( EPA ), an n 3 fatty acid, on TCDD ‐induced toxicity. Experimental Approach In cultures of HepG2 cells, the EPA / AA ratio was determined using gas chromatography, oxidative stress and inflammatory responses through reactive oxygen species ( ROS ) levels, antioxidant status, [ Ca 2+ ] i , nuclear migration of two redox‐sensitive transcription factors, NF ‐κ B p65 and N rf‐2, expression of MAP kinase (p‐ E rk, p‐p38), NF ‐κ B p65, COX ‐2 and N rf‐2. Cellular changes in ΔΨm, acidic vesicular organelle formation, cell cycle analysis and scanning electron microscopy analysis were performed. Key ResultsEPA offered significant cytoprotection by increasing EPA / AA ratios in cell membranes, inhibiting ROS generation, enhancing antioxidant status and modulating nuclear translocation of redox‐sensitive transcription factors ( NF ‐κ B p65 and N rf‐2) and expression of NF ‐κB p65, COX ‐2 and N rf‐2. Furthermore, TCDD ‐induced upstream events of MAPK phosphorylation, the increase in [ Ca 2+ ] i levels and cell surface changes in microvilli were significantly inhibited by EPA . EPA treatment maintained ΔΨm and prevented formation of acidic vesicular organelles. Conclusion and Implications The present study demonstrates for the first time some underlying molecular mechanisms of cytoprotection exerted by EPA against TCDD ‐induced oxidative stress and inflammatory responses.