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

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 toxicity via protecting mitochondria through its antioxidant potential. The present investigation based on mitochondria reveals the probability of cardioprotective potential of phloretin for the cancer patients on ATO chemotherapy.

• Authors: Vadavanath Prabhakaran Vineetha, Rema Sreenivasan Soumya, Kozhiparambil Gopalan Raghu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 754 Pg. 162-72 (May 05 2015) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 25746422 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antioxidants
• Arsenicals
• Electron Transport Chain Complex Proteins
• Oxides
• Reactive Oxygen Species
• Superoxides
• Adenosine Triphosphate
• Phloretin
• Arsenic Trioxide
• Calcium

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Arsenic Trioxide
• Arsenicals (adverse effects)
• Calcium (metabolism)
• Cell Membrane Permeability (drug effects)
• Cells, Cultured
• Electron Transport Chain Complex Proteins (metabolism)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism, pathology)
• Myoblasts (drug effects, pathology)
• Myocytes, Cardiac (drug effects, pathology)
• Oxidative Stress (drug effects)
• Oxides (adverse effects)
• Oxygen Consumption (drug effects)
• Phloretin (pharmacology)
• Rats
• Reactive Oxygen Species (metabolism)
• Superoxides (metabolism)