Polyphenol-rich apple (Malus domestica L.) peel extract attenuates arsenic trioxide induced cardiotoxicity in H9c2 cells via its antioxidant activity

Abstract

Evidences suggest that apple peel has a wide range of polyphenols having antioxidant activity and its consumption has been linked with improved health benefits. Arsenic trioxide (ATO) is a very effective drug for the treatment of acute promyelocytic leukemia (APL) but it leads to cardiotoxicity mediated through alterations in various cardiac ion channels and by increasing the intracellular calcium level and reactive oxygen species (ROS). The aim of the present investigation was to study the effect of methanolic extract of apple peel (APME) and aqueous extract of apple peel (APAE) on ATO (5 μM) induced toxicity in the H9c2 cardiac myoblast cell line. We estimated the cellular status of innate antioxidant enzymes, level of ROS, mitochondrial superoxide, glutathione and intracellular calcium with ATO and apple peel extracts. Prior to the cell line based study, we had evaluated the antioxidant potential of apple peel extract by 1,1-diphenyl-2-picrylhydrazyl (DPPH), total reducing power (TRP), superoxide anion and hydroxyl radical scavenging activity, in addition to quantifying total phenolic and flavonoid content. Both the extracts showed considerable antioxidant activity in cell-free chemical assays. In addition, both APME and APAE prevented the alteration in antioxidant status induced by ATO in H9c2 cells. Significant differential alterations had been observed in the activity of lactate dehydrogenase, superoxide dismutase, catalase, glutathione, glutathione peroxidase, thioredoxin reductase, xanthine oxidase, calcium overload and caspase 3 activity with ATO. The overall result revealed the protective property of polyphenol-rich apple peel extract against ATO induced cardiac toxicity via its antioxidant activity.

Salvianolic Acid A Protects H9c2 Cells from Arsenic Trioxide-Induced Injury via Inhibition of the MAPK Signaling Pathway

“…In line with previous reports, we showed that ATO treatment can increase ROS production and decrease antioxidant enzyme activity in cardiomyocytes. Therefore, ATO induces oxidative stress in myocardial cells by producing ROS and inhibiting the intrinsic protective antioxidant capacity [29-31]. Consequently, a compound that can decrease ROS overproduction and also prevent cardiomyocyte apoptosis is of great interest to improve the adverse effects of ATO.…”

Protective Effect of Boerhaavia diffusa L. against Mitochondrial Dysfunction in Angiotensin II Induced Hypertrophy in H9c2 Cardiomyoblast Cells

“…Various epidemiological, experimental and clinical studies have revealed that natural products in the form of functional foods or nutracuticals play an important role in the prevention and management of cardiac diseases in prophylactic way [10], [11]. High consumption of plant-based foods is associated with a significantly lower risk of coronary artery disease most likely due to the abundance and variety of bioactive compounds present in it [12], [13]. Besides antioxidant activity, natural products have other biological properties like lipid lowering, antihyperglycemic, antihypertensive etc.…”

Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells

“…Activation of c‐Jun NH 2 ‐terminal kinase and disruption of microtubule are generally involved (Goussetis et al, ). In addition, arsenic trioxide is able to induce apoptosis in many different kinds of cancer or noncancer cells (Chen et al, ; Huang et al, ; Yedjou et al, ; Nakamura et al, ; Selvaraj et al, ; Vineetha et al, ; Mandegary et al, ). It is noteworthy that the complete remission rate of arsenic trioxide treatment is about 85% (29 of 34 patients) in relapsed APL (Kwong et al, ).…”