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

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

• Tipo de documento: Artigo Científico
• Fonte: HELIYON; v. 10, n. 17, p. 11-pg., 2024-09-15.

Resumo

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 aim is to evaluate the effects of Pera orange juice (Citrus sinensis L. Osbeck) on mitigating lipid metabolism imbalance, metabolic pathways, and DOX induced cytotoxic effects in the heart and liver. 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 gamma (PPAR gamma 1) in the heart, and reduced carnitine palmitoyltransferase I (CPT1) in the liver. 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. (AU)

• Processo FAPESP: 21/09517-2 - Avaliação do papel da administração de suco de laranja na dislipidemia e nas alterações hepáticas e cardíacas induzidas pela doxorrubicina em ratos
• Beneficiário: Ronny Peterson Cabral Filho
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 22/15954-9 - Influência de análogo de GLP-1 na microbiota intestinal e atenuação da cardiotoxicidade induzida pela doxorrubicina em ratos
• Beneficiário: Sergio Alberto Rupp de Paiva
• Modalidade de apoio: Auxílio à Pesquisa - Regular