Nutritional leucine supplementation attenuates cardiac failure in tumour-bearing cachectic animals

Autor(es)

Toneto, Aline Tatiane ; Ferreira Ramos, Luiz Alberto ; Salomao, Emilianne Miguel ; Tomasin, Rebeka ; Aereas, Miguel Arcanjo ; Cintra Gomes-Marcondes, Maria Cristina

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE; v. 7, n. 5, p. 577-586, DEC 2016.
• Citações Web of Science: 16

Resumo

Background The condition known as cachexia presents in most patients with malignant tumours, leading to a poor quality of life and premature death. Although the cancer-cachexia state primarily affects skeletal muscle, possible damage in the cardiac muscle remains to be better characterized and elucidated. Leucine, which is a branched chain amino acid, is very useful for preserving lean body mass. Thus, this amino acid has been studied as a coadjuvant therapy in cachectic cancer patients, but whether this treatment attenuates the effects of cachexia and improves cardiac function remains poorly understood. Therefore, using an experimental cancer-cachexia model, we evaluated whether leucine supplementation ameliorates cachexia in the heart. Methods Male Wistar rats were fed either a leucine-rich or a normoprotein diet and implanted or not with subcutaneous Walker-256 carcinoma. During the cachectic stage (approximately 21days after tumour implantation), when the tumour mass was greater than 10% of body weight, the rats were subjected to an electrocardiogram analysis to evaluate the heart rate, QT-c, and T wave amplitude. The myocardial tissues were assayed for proteolytic enzymes (chymotrypsin, alkaline phosphatase, cathepsin, and calpain), cardiomyopathy biomarkers (myeloperoxidase, tissue inhibitor of metalloproteinases, and total plasminogen activator inhibitor 1), and caspase-8, -9, -3, and -7 activity. Results Both groups of tumour-bearing rats, especially the untreated group, had electrocardiography alterations that were suggestive of ischemia, dilated cardiomyopathy, and sudden death risk. Additionally, the rats in the untreated tumour-bearing group but not their leucine-supplemented littermates exhibited remarkable increases in chymotrypsin activity and all three heart failure biomarkers analysed, including an increase in caspase-3 and -7 activity. Conclusions Our data suggest that a leucine-rich diet could modulate heart damage, cardiomyocyte proteolysis, and apoptosis driven by cancer-cachexia. Further studies must be conducted to elucidate leucine's mechanisms of action, which potentially includes the modulation of the heart's inflammatory process. (AU)

• Processo FAPESP: 10/00714-5 - "Estudo dos Efeitos Modulatórios da Aloe vera e mel sobre o crescimento tumoral"
• Beneficiário: Rebeka Tomasin
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/16115-1 - Estudo dos mecanismos bioquímicos e moleculares da caquexia: avaliação dos efeitos do fator Walker (FW) e da leucina em cultura celular de miotúbulos (células C2C12)
• Beneficiário: Maria Cristina Cintra Gomes Marcondes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/00209-9 - Nutrição e câncer estudo das alterações metabólicas e moleculares do metabolismo protéico no câncer-caquexia, moduladas pela suplementação nutricional com leucina, no crescimento, desenvolvimento e gravidez
• Beneficiário: Maria Cristina Cintra Gomes Marcondes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/11993-5 - Atividade física e suplementação nutricional de leucina associadas ao crescimento tumoral: estudo do perfil hormonal de ratos implantados com carcinossarcoma de Walker 256
• Beneficiário: Aline Tatiane Toneto
• Modalidade de apoio: Bolsas no Brasil - Mestrado