Phloretin ameliorates arsenic trioxide induced mitochondrial dysfunction in H9c2 cardiomyoblasts mediated via alterations in membrane permeability and ETC complexes

European Journal of Pharmacology
Vadavanath Prabhakaran VineethaKozhiparambil Gopalan Raghu

Abstract

Arsenic trioxide (ATO), though a very effective drug for the treatment of acute promyelocytic leukemia, leads to cardiotoxicity. As mitochondria are the center of attention of cardiac cell׳s general metabolic status, it is primarily important to see the interaction of ATO with mitochondria. Studies related exclusively to the alterations in mitochondria and its associated functions caused by ATO are very limited. The present investigation aims to explore the effect of ATO on various components of electron transport chain, oxygen consumption, ATP production, mitochondrial superoxide generation, transmembrane potential, permeability pore opening, calcium homeostasis and apoptosis. Attempts were also made to see the efficacy of phloretin, a potent antioxidant flavonoid found majorly in apple peel on cardiotoxicity. The H9c2 cells exposed to ATO (5µM) exhibited increased oxidative stress with reduced innate antioxidant status, mitochondrial dysfunctions and apoptosis. It increased the intracellular calcium content, caused alterations in the activity of transcription factor Nrf2, xanthine oxidase, aconitase and caspase 3 compared to the control group. Phloretin at 2.5 and 5µM concentrations were able to protect the cells from ATO tox...Continue Reading

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Citations

Mar 16, 2016·Pharmacology Research & Perspectives·Fabienne Foufelle, Bernard Fromenty
Apr 4, 2017·The Plant Journal : for Cell and Molecular Biology·Andrew P DareRoss G Atkinson
Jan 9, 2019·Cardiovascular Toxicology·Vadavanath Prabhakaran Vineetha, Kozhiparambil Gopalan Raghu
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Apr 11, 2018·World Journal of Gastroenterology : WJG·Hui YeFrancisco Javier Cubero
Sep 16, 2017·Journal of Food and Drug Analysis·Shih-Hsin TuYuan-Soon Ho
Jun 26, 2020·Frontiers in Cell and Developmental Biology·Wanjun MaWenqun Li
Jan 8, 2021·Environmental Science and Pollution Research International·Gyanendra SinghDharati Parmar

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