Omega-3 supplementation attenuates doxorubicin-induced cardiotoxicity but is not related to the ceramide pathway

Autor(es):Mostrar menos -

Monte, Marina Gaiato ; Tonon, Carolina Rodrigues ; Fujimori, Anderson Seiji ; Ribeiro, Ana Paula Dantas ; Zanati, Silmeia Garcia ; Okoshi, Katashi ; Camacho, Camila Renata Correa ; Moretto, Maria Regina ; de Paiva, Sergio Alberto Rupp ; Zornoff, Leonardo Antonio Mamede ; Azevedo, Paula Schmidt ; Minicucci, Marcos Ferreira ; Polegato, Bertha Furlan

• Tipo de documento: Artigo Científico
• Fonte: FOOD SCIENCE & NUTRITION; v. N/A, p. 14-pg., 2024-09-29.

Resumo

Cardiotoxicity is the serious side effect of doxorubicin treatment. Ceramides are formed from the degradation of sphingolipids in cell membranes and play an important role in signaling and modulating biological processes. There is evidence that omega-3 fatty acid administration can act on this pathway. To evaluate the role of the ceramide pathway in the pathophysiology of doxorubicin-induced cardiotoxicity and the effect of omega-3 fatty acid supplementation in the attenuation of chronic doxorubicin-induced cardiotoxicity in rats. Sixty male Wistar rats were divided into four groups: Control (C), Doxorubicin (D), Omega-3 fatty acids (W), and Doxorubicin + Omega-3 fatty acids (DW). The groups received omega-3 fatty acids (400 mg/kg/day, via gavage) or water for 6 weeks and doxorubicin (3.5 mg/kg, intraperitoneal) or saline once a week for 4 weeks. Doxorubicin-treated animals showed increases in left atrium and left ventricle diameters, serum triglycerides and cholesterol, malondialdehyde, and protein carbonylation. We also observed a decrease in left ventricular shortening fraction and nSMase1 expression in the heart. Omega-3 fatty acid supplementation attenuated the structural and functional alterations caused by doxorubicin and decreased protein carbonylation. In contrast to doxorubicin, omega-3 fatty acids increased neutral nSMase activity in animals that both received and did not receive doxorubicin but with no effect on nSMase1 protein expression. Omega-3 fatty acid supplementation attenuated the cardiotoxicity caused by doxorubicin. The ceramide pathway may be involved in the pathophysiology of cardiotoxicity, but it is not the mechanism by which omega-3 fatty acids attenuated cardiac dysfunction. This is experimental research that showed the effect of omega-3 fatty acids administration on cardiac toxicity induced by doxorubicin. Interestingly, the omega-3 mitigated the deleterious effect of doxorubicin in the heart, but it did not affect the ceramide pathway, that was our original hypothesis. DOXO: doxorubicin; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; LVFS: LV fraction shortening; LAD: left atrium diameter; LV: left ventricle; MDA: malondialdehyde; nSMases: neutral sphingomyelinase; TG: triglycerides.image (AU)

• Processo FAPESP: 18/25677-7 - Influência da suplementação de ômega 3 na atenuação da cardiotoxicidade induzida pela doxorrubicina em ratos: papel da via da ceramida
• Beneficiário: Marina Gaiato Monte
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• 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