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

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.

The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence

“…Among flavanones, hesperidin is an antioxidant that can be typically found in citrus fruits [ 295 ]. Its properties impact positively on cardiomyocytes as it attenuates senescence-related oxidative damage, both independently and in combination with other molecules, through the induction of Nrf2 and of GST expression [ 247 , 296 , 297 ]. Citrus juice, which is rich in hesperidin and other flavanones as well as in flavones, anthocyanins, and other molecules, was reported to reduce ROS levels and reduce SA-β gal positive HUVEC [ 298 ].…”

Protective role of hesperidin against γ-radiation-induced oxidative stress and apoptosis in rat testis

“…had no side effect. On the other hand, it has been reported that the regular consumption of flavonoid-containing foods can reduce the risk of diseases [ 30 ]. In addition, the results of the present study showed that the administration of rats with H which dissolved in DMSO (H group) caused non significant ( p > 0.05) changes in some biochemical parameters and relative testis/body weight ratios as compared with the C group and this may be due to the effect of DMSO.…”

Citrus sinensis and Vitis vinifera Protect Cardiomyocytes from Doxorubicin-Induced Oxidative Stress: Evaluation of Onconutraceutical Potential of Vegetable Smoothies

“…In addition, hesperitin, the aglycone of hesperidin, has a cardioprotective effect increasing GHS levels and preventing oxidative DNA damage in rat models [35]. Furthermore, has been reported that Pummelo (Citrus maxima) phytocomplex exert protection in cardiomyocytes by reduction of intracellular oxidative stress, maintaining GSH availability, and enhancing GST enzyme activity and expression in rat cardiac cells [36].…”