Pera orange (Citrus sinensis) and Moro orange (Citrus sinensis (L.) Osbeck) juices attenuate left ventricular dysfunction and oxidative stress and improve myocardial energy metabolism in acute doxorubicin-induced cardiotoxicity in rats

Abstract

Objectives: Doxorubicin is a highly effective chemotherapeutic agent for treating several types of cancer; however, it can induce cardiotoxicity. We evaluated the influence of Pera and Moro orange juices on cardiac remodeling induced by acute administration of doxorubicin in rats. Methods: We allocated 120 male Wistar rats into six groups: control (C), Pera orange juice (PO), Moro orange juice (MO), doxorubicin (D), doxorubicin + Pera orange juice (DPO), and doxorubicin + Moro orange juice (DMO). Groups PO and DPO received Pera orange juice, MO and DMO received Moro orange juice, and C and D received water with maltodextrin (100 g/L) for 4 wk. Subsequently, groups D, DPO, and DMO received 20 mg/kg doxorubicin and C, PO, and MO received saline. Echocardiogram and euthanasia were performed 48 h after doxorubicin injection. Juice and animal-serum flavonoid identification and quantification were evaluated by liquid chromatography/electrospray ionization multistage mass spectrometry. Oxidative stress and myocardial metabolism were evaluated by spectrophotometry. Results: Systolic and diastolic left ventricular dysfunction increased oxidative stress and pathologic changes in myocardial energy metabolism of rats treated with doxorubicin. Intake of both orange juices improved left ventricular function, decreased oxidative stress, and attenuated the myocardial energy metabolism changes. Moro orange juice had a more pronounced effect than Pera orange juice in glutathione peroxidase activity, citrate synthase, and β-hydroxyacyl-CoA dehydrogenase activity. Conclusions: Pera and Moro orange juices attenuated cardiac remodeling induced by doxorubicin, improved myocardial energy metabolism, and attenuated oxidative stress. However, Moro orange juice was more effective than Pera orange juice in modifying energy metabolism.