Pummelo Protects Doxorubicin-Induced Cardiac Cell Death by Reducing Oxidative Stress, Modifying Glutathione Transferase Expression, and Preventing Cellular Senescence

L Chularojmontri,S K Wattanapitayakul,O Gerdprasert

doi:10.1155/2013/254835

L Chularojmontri, S K Wattanapitayakul + Show 1 more

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https://doi.org/10.1155/2013/254835

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Abstract

Citrus flavonoids have been shown to reduce cardiovascular disease (CVD) risks prominently due to their antioxidant effects. Here we investigated the protective effect of pummelo (Citrus maxima, CM) fruit juice in rat cardiac H9c2 cells against doxorubicin (DOX-) induced cytotoxicity. Four antioxidant compositions (ascorbic acid, hesperidin, naringin, and gallic acid) were determined by HPLC. CM significantly increased cardiac cell survival from DOX toxicity as evaluated by MTT assay. Reduction of cellular oxidative stress was monitored by the formation of DCF fluorescent product and total glutathione (GSH) levels. The changes in glutathione-S-transferase (GST) activity and expression were determined by enzyme activity assay and Western blot analysis, respectively. Influence of CM on senescence-associated β-galactosidase activity (SA-β-gal) was also determined. The mechanisms of cytoprotection involved reduction of intracellular oxidative stress, maintaining GSH availability, and enhanced GST enzyme activity and expression. DOX-induced cellular senescence was also attenuated by long-term CM treatment. Thus, CM fruit juice can be promoted as functional fruit to protect cells from oxidative cell death, enhance the phase II GSTP enzyme activity, and decrease senescence phenotype population induced by cardiotoxic agent such as DOX.

Highlights

Belonging to anthracyclines, doxorubicin (DOX) is an anticancer drug widely used to treat many types of cancer but the dose-dependent cardiotoxic adverse effect limits its full clinical value [1]
It is well recognized that DOX-induced cardiotoxicity occurs through multiple mechanisms which involve oxidative stress generated by quinone moiety of the anthracycline structure. e redox recycling of semiquinone and its parent quinone is known to generate reactive oxygen species (ROS) leading to mitochondria dysfunction, myocyte senescence, and apoptosis, and causing cardiac remodeling and contractility impairment [2, 3]
Our study demonstrated that pummelo fruit juice (Citrus maxima (Burm.f.) Merr., coincubation with pummelo (CM)) protected against DOX-induced cardiotoxicity in H9c2 via mechanisms related to the reduction of cellular oxidative stress, enhancement of GSH antioxidant pool, and increase of the detoxifying enzyme GSTP activity and expression

Summary

Introduction

Belonging to anthracyclines, doxorubicin (DOX) is an anticancer drug widely used to treat many types of cancer but the dose-dependent cardiotoxic adverse effect limits its full clinical value [1]. It is well recognized that DOX-induced cardiotoxicity occurs through multiple mechanisms which involve oxidative stress generated by quinone moiety of the anthracycline structure. Among several attempts initiated to decrease cardiotoxic adverse effect of this valuable drug, scavenging of ROS by natural antioxidants demonstrates favorable cardioprotective effect against DOX-induced cardiotoxicity both in vitro and in vivo [4, 5]. Ai pummelo fruit juices contain high antioxidants and scavenging property against free radicals [7], but their potential properties as cytoprotective nutrients against oxidative cell death, DOX toxicity, has not been explored Belonging to the Citrus family, pummelo fruits are indigenous to the oriental areas such as ailand, China, Japan, and India. ai pummelo fruit juices contain high antioxidants and scavenging property against free radicals [7], but their potential properties as cytoprotective nutrients against oxidative cell death, DOX toxicity, has not been explored

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