Pera orange juice (Citrus sinensis L. Osbeck) alters lipid metabolism and attenuates oxidative stress in the heart and liver of rats treated with doxorubicin

佩拉橙汁 (Citrus sinensis L. Osbeck) 可改变接受阿霉素治疗的大鼠的脂质代谢并减轻其心脏和肝脏的氧化应激

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作者:Ronny Peterson Cabral, Ana Paula Dantas Ribeiro, Marina Gaiato Monte, Anderson Seiji Soares Fujimori, Carolina Rodrigues Tonon, Natalia Fernanda Ferreira, Silmeia Garcia Zanatti, Marcos Ferreira Minicucci, Leonardo Antonio Mamede Zornoff, Sergio Alberto Rupp de Paiva, Bertha Furlan Polegato

Background

Doxorubicin (DOX) is a highly effective chemotherapy drug widely used to treat cancer, but its use is limited due to multisystemic toxicity. Lipid metabolism is also affected by doxorubicin. Orange juice can reduce dyslipidemia in other clinical situations and has already been shown to attenuate cardiotoxicity. Our

Conclusion

DOX caused dyslipidemia, liver and cardiac toxicity by increasing oxidative stress, and altered energy metabolic parameters in both organs. Despite not improving changes in left ventricular morphology, orange juice did attenuate oxidative stress and mitigate the metabolic effects of DOX.

Methods

Twenty-four male Wistar rats were allocated into 3 groups: Control (C); DOX (D); and DOX plus Pera orange juice (DOJ). DOJ received orange juice for 4 weeks, while C and D received water. At the end of each week, D and DOJ groups received 4 mg/kg/week DOX, intraperitoneal. At the end of 4 weeks animals were submitted to echocardiography and euthanasia.

Results

Animals treated with DOX decreased water intake and lost weight over time. At echocardiography, DOX treated rats presented morphologic alterations in the heart. DOX increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, high density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides. It also reduced superoxide dismutase (SOD) activity, increased protein carbonylation in the heart and dihydroethidium (DHE) expression in the liver, decreased glucose transporter type 4 (GLUT4) and the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ1) in the heart, and reduced carnitine palmitoyltransferase I (CPT1) in the liver.

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