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

Author(s)

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

• Document type: Journal article
• Source: JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE; v. 7, n. 5, p. 577-586, DEC 2016.
• Web of Science Citations: 16

Abstract

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)

• FAPESP's process: 10/00714-5 - "Modulatory Effects of Aloe vera and honey in tumour growth"
• Grantee: Rebeka Tomasin
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/16115-1 - Biochemical and molecular mechanisms of cachexia. effects of Walker factor and leucine supplementation on myotube cell culture
• Grantee: Maria Cristina Cintra Gomes Marcondes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/00209-9 - Nutritional supplementation and cancer cachexia. Biochemical and molecular studies
• Grantee: Maria Cristina Cintra Gomes Marcondes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/11993-5 - Hormonal profile in tumour-bearing rats submitted to leucine-rich diet and physical exercise
• Grantee: Aline Tatiane Toneto
• Support Opportunities: Scholarships in Brazil - Master