Wheat phenolics suppress doxorubicin-induced cardiotoxicity via inhibition of oxidative stress, MAP kinase activation, NF-κB pathway, PI3K/Akt/mTOR impairment, and cardiac apoptosis. (March 2019)

• Record Type: Journal Article
• Authors: Sahu, Ranabir; Dua, Tarun K.; Das, Sonjit; De Feo, Vincenzo; Dewanjee, Saikat
• Is Part Of: Food and chemical toxicology. Volume 125(2019)
• Page Start: 503
• Page End: 519
• Publication Date: 2019-03
• Subjects: Apoptosis -- Cardiomyopathy -- Doxorubicin -- Oxidative stress -- Wheat phenolics -- Whole wheat grains; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2019.01.034
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: 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 μM) 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-κB, 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. Highlights: Polyphenolics extract of whole wheat grains attenuated doxorubicin induced cardio-toxicity. Ferulic acid and apigenin were found to be the most abundant phenolic and flavonoid in the extract, respectively. The extract attenuated doxorubicin induced oxidative stress and apoptosis via multiple mechanisms. The extract reciprocated doxorubicin-induced alteration in MAP kinases/NF-κB/PI3K/Akt/mTOR signaling. The extract exhibited better cardio-protective effect over ferulic acid and apigenin.