Sunday, October 04, 2015 9:17:20 AM
Palanisamy K1,2, Krishnaswamy R3, Paramasivan P1, Chih-Yang H4,5,6, Vishwanadha VP1,4,7.
Author information
Abstract
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 n3 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-?B p65 and Nrf-2, expression of MAP kinase (p-Erk, p-p38), NF-?B p65, COX-2 and Nrf-2. Cellular changes in ??m, acidic vesicular organelle formation, cell cycle analysis and scanning electron microscopy analysis were performed.
KEY RESULTS:
EPA 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-?B p65 and Nrf-2) and expression of NF-?B p65,COX-2 and Nrf-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 ??m 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.
© 2015 The British Pharmacological Society.
PMID:
http://www.ncbi.nlm.nih.gov/pubmed/26177858
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