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

Ribeiro, Ana Paula Dantas; Pereira, Amanda Gomes; Todo, Márcia Cristina; Fujimori, Anderson Seiji Soares; Santos, Priscila P.; Dantas, Danielle; Fernandes, Ana Angélica Henrique; Zanati, Silméia Garcia; Hassimotto, Neuza Mariko Aymoto; Zornoff, Leonardo Antônio Mamede; Azevedo, Paula Schmidt; Minicucci, Marcos F.; Paiva, Sérgio Alberto Rupp de; Polegato, Bertha Furlan

doi:10.1016/j.nut.2021.111350

Cited by 14 publications

(11 citation statements)

References 39 publications

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“…Cardiac injury leads to a shift in heart energy metabolism; the myocardium starts to use mainly glucose to generate ATP because it is less costly for the tissue than fatty acids. Concerning this, Dox treatment increased the activity of enzymes related to glucose metabolism (phosphofructokinase and lactate dehydrogenase) and decreased the activity of enzymes related to lipid metabolism (β-hydroxyacyl Co-A dehydrogenase) as well as citrate synthase activity (the first enzyme of the Krebs cycle) and ATP synthase of the mitochondrial phosphorylation, as demonstrated in our previous studies [ 5 , 31 ]. The administration of doxycycline attenuated these metabolic alterations, bringing the myocardial metabolism closer to the physiological situation; we observed an improvement in the activity of lactate dehydrogenase, β-hydroxyacyl Co-A dehydrogenase, citrate synthase, and ATP synthase.…”

Section: Discussionsupporting

confidence: 72%

Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in Rats

Dantas

Pereira

Fujimori

et al. 2022

JCDD

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Aim: Evaluate the influence of doxycycline, an anti-inflammatory and matrix metalloproteinase (MMP) inhibitor, on the attenuation of chronic doxorubicin-induced cardiotoxicity in rats. Methods: We allocated male Wistar rats into four groups: control (C), doxorubicin (D), doxycycline (inhibitor of MMP, IM), and Dox + doxycycline (DIM). Groups IM and DIM received doxycycline (5 mg/kg, IP) once a week for 4 weeks. In addition, 48 h after every doxycycline injection, groups D and DIM received Dox (5 mg/kg, IP). We performed echocardiogram and evaluated TIMP-4 and collagen I protein expression, MMP-2 activity, and oxidative stress and myocardial metabolism. Results: Doxorubicin promotes left atrium (LA) and left ventricle (LV) dilatation and decreases in LV fractional shortening, which was improved by doxycycline. Moreover, doxycycline attenuated the LV cardiomyocyte hypertrophy and collagen type I expression. Doxorubicin increased phosphofructokinase and decreased beta-hydroxyacyl Co-A dehydrogenase, pyruvate dehydrogenase, citrate synthase, and ATP synthase activity, which was partially attenuated by doxycycline. Lastly, doxycycline improved antioxidant enzyme activity in the DIM group. Conclusion: Doxorubicin increases oxidative stress and promotes changes in myocardial energy metabolism, accompanied by structural and functional changes. Doxycycline attenuated the doxorubicin-induced cardiotoxicity, at least in part, through changes in myocardial energy metabolism.

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Section: Discussionsupporting

confidence: 72%

Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in Rats

Dantas

Pereira

Fujimori

et al. 2022

JCDD

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“…This notion is supported by the reports which showed that a single Dox injection in C57BL/6 mice can lead to significant increases E/E’ ratios at 5 to 12 week time points after drug treatment compared to controls [ 62 , 63 , 64 ]. The diastolic dysfunction was shown to occur as early as 2 days after Dox injection in a rat model [ 65 ]. However, a recent meta-analysis showed that anthracycline-chemotherapy in breast cancer patients without previous cardiac disease had a modest early impact on E/A and E/E’ ratios [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Transplanted Cell Homing by FGF1 and PDGFB after Doxorubicin Myocardial Injury

Baguma-Nibasheka

Feridooni

Zhang

et al. 2021

Cells

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There is no effective treatment for the total recovery of myocardial injury caused by an anticancer drug, doxorubicin (Dox). In this study, using a Dox-induced cardiac injury model, we compared the cardioprotective effects of ventricular cells harvested from 11.5-day old embryonic mice (E11.5) with those from E14.5 embryos. Our results indicate that tail-vein-infused E11.5 ventricular cells are more efficient at homing into the injured adult myocardium, and are more angiogenic, than E14.5 ventricular cells. In addition, E11.5 cells were shown to mitigate the cardiomyopathic effects of Dox. In vitro, E11.5 ventricular cells were more migratory than E14.5 cells, and RT-qPCR analysis revealed that they express significantly higher levels of cytokine receptors Fgfr1, Fgfr2, Pdgfra, Pdgfrb and Kit. Remarkably, mRNA levels for Fgf1, Fgf2, Pdgfa and Pdgfb were also found to be elevated in the Dox-injured adult heart, as were the FGF1 and PDGFB protein levels. Addition of exogenous FGF1 or PDGFB was able to enhance E11.5 ventricular cell migration in vitro, and, whereas their neutralizing antibodies decreased cell migration. These results indicate that therapies raising the levels of FGF1 and PDGFB receptors in donor cells and or corresponding ligands in an injured heart could improve the efficacy of cell-based interventions for myocardial repair.

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“…In animal studies of our review, polyphenols were defined as a broad class of compounds with multiple phenolic hydroxyls (PhOH) and were reported in 29 studies ( 38 – 66 ). These covered proanthocyanidin ( n = 6, all derived from grape seed extract) ( 38 – 43 ), anthocyanin ( n = 1, derived from purple corn) ( 44 ), resveratrol ( n = 2) ( 45 , 46 ), curcumin ( n = 5) ( 47 – 51 ), catechins ( n = 3, derived from green tea and black tea) ( 52 – 54 ), and mixed phenolic compounds extracted from local products [ n = 12, derived from date ( 55 , 56 ), orange ( 57 ), cranberry ( 58 ), cardamom ( 59 ), pomegranate ( 60 ), hawthorn ( 61 ), naringenin ( 62 ), p-coumaric acid ( 63 ), honey ( 64 ), yogurt ( 65 ) and yellow wine ( 66 )]. Three studies demonstrated that supplementation of polyphenols could improve DOX-induced cardiac dysfunctions evaluated by echocardiography ( 45 , 57 , 66 ).…”

Section: Resultsmentioning

confidence: 99%

“…These covered proanthocyanidin ( n = 6, all derived from grape seed extract) ( 38 – 43 ), anthocyanin ( n = 1, derived from purple corn) ( 44 ), resveratrol ( n = 2) ( 45 , 46 ), curcumin ( n = 5) ( 47 – 51 ), catechins ( n = 3, derived from green tea and black tea) ( 52 – 54 ), and mixed phenolic compounds extracted from local products [ n = 12, derived from date ( 55 , 56 ), orange ( 57 ), cranberry ( 58 ), cardamom ( 59 ), pomegranate ( 60 ), hawthorn ( 61 ), naringenin ( 62 ), p-coumaric acid ( 63 ), honey ( 64 ), yogurt ( 65 ) and yellow wine ( 66 )]. Three studies demonstrated that supplementation of polyphenols could improve DOX-induced cardiac dysfunctions evaluated by echocardiography ( 45 , 57 , 66 ). LVEF significantly reduced in DOX groups, but was similar in DOX+Nutrients groups and control groups.…”

Section: Resultsmentioning

confidence: 99%

Can Dietary Nutrients Prevent Cancer Chemotherapy-Induced Cardiotoxicity? An Evidence Mapping of Human Studies and Animal Models

Zhang

Yang²,

Li³

et al. 2022

Front. Cardiovasc. Med.

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IntroductionChemotherapy has significantly improved cancer survival rates at the cost of irreversible and frequent cardiovascular toxicity. As the main dose-dependent adverse effect, cardiotoxic effects not only limit the usage of chemotherapeutic agents, but also cause the high risk of severe poor prognoses for cancer survivors. Therefore, it is of great significance to seek more effective cardioprotective strategies. Some nutrients have been reported to diminish cardiac oxidative damage associated with chemotherapy. However, the currently available evidence is unclear, which requires a rigorous summary. As such, we conducted a systematic review of all available evidence and demonstrated whether nutrients derived from food could prevent cardiotoxicity caused by chemotherapy.MethodsWe searched Medline (via PubMed), Embase and the Cochrane Library from inception to Nov 9, 2021 to identify studies reporting dietary nutrients against cancer chemotherapy-related cardiotoxicity. We performed descriptive summaries on the included studies, and used forest plots to demonstrate the effects of various dietary nutrients.ResultsFifty-seven eligible studies were identified, involving 53 animal studies carried on rats or mice and four human studies in cancer patients. Seven types of dietary nutrients were recognized including polyphenols (mainly extracted from grapes, grape seeds, and tea), allicin (mainly extracted form garlic), lycopene (mainly extracted from tomatoes), polyunsaturated fatty acids, amino acids (mainly referring to glutamine), coenzyme Q10, and trace elements (mainly referring to zinc and selenium). Dietary nutrients ameliorated left ventricular dysfunctions and myocardial oxidative stress at varying degrees, which were caused by chemotherapy. The overall risk of bias of included studies was at moderate to high risk.ConclusionThe results indicated that dietary nutrients might be a potential strategy to protect cardiovascular system exposed to the chemotherapeutic agents, but more human studies are urged in this field.Systematic Review Registration:https://inplasy.com/inplasy-2022-3-0015/.

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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

Cited by 14 publications

References 39 publications

Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in Rats

Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in Rats

Regulation of Transplanted Cell Homing by FGF1 and PDGFB after Doxorubicin Myocardial Injury

Can Dietary Nutrients Prevent Cancer Chemotherapy-Induced Cardiotoxicity? An Evidence Mapping of Human Studies and Animal Models

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