Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 125, Issue -, Pages 503-519Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2019.01.034
Keywords
Apoptosis; Cardiomyopathy; Doxorubicin; Oxidative stress; Wheat phenolics; Whole wheat grains
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Funding
- Council of Scientific & Industrial Research (CSIR), New Delhi, India [02(0275)/16/EMR-II]
- University Grants Commission (UGC), New Delhi [F1-17.1/2013-14/RGNF-2013-14-SC-ASS-52029 (SA-III/Website), F./PDFSS-2013-14-ST-WES-6992]
- University of Salerno, Salerno, Italy
- Jadavpur University, Kolkata, India
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The present investigation has been undertaken to reveal the protective mechanism of polyphenolics extract of whole wheat grains (WWGPE), ferulic acid and apigenin against doxorubicin (Dox)-induced cardio-toxicity. WWGPE, apigenin, and ferulic acid exhibited concentration dependent cyto-protective effect against Dox (1 0) in rat cardiomyocytes. Dox treatment significantly (p < 0.01) induced oxidative stress in the myocardial cells via excessive ROS production, increase in iNOS expression, NADPH oxidase activation, Nrf-2/HO-1 impairment, and inactivation of cellular redox defense system. In addition, Dox significantly (p < 0.01) activated MAP kinases, NF-kappa B, and apoptosis in cardiac cells; while, significant (p < 0.01) impairment in PI3K/Akt/mTOR signaling was observed in Dox-treated myocardial cells. On the other hand, WWGPE, apigenin, and ferulic acid significantly (p < 0.05-0.01) attenuated Dox-induced redox stress and oxidative stress-mediated signal transduction in myocardial cells. WWGPE, apigenin, and ferulic acid treatment also could significantly (p < 0.05-0.01) reinstate Dox-mediated changes in blood parameters in rats. Histological assessments were in agreement with the biochemical findings. Results showed that, WWGPE exhibited better cardio-protective effect over ferulic acid and apigenin, which may be due to the synergy between the comprising compounds and better oral bioavailability of dietary antioxidant molecules from whole phenolic extract.
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