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

Abstract

BackgroundThe 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.MethodsMale 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 21 days 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.ResultsBoth 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.ConclusionsOur 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.

Collagen‐induced arthritis as an animal model of rheumatoid cachexia

“…There are many animal models in which muscle loss is observed as a result of the disease development. There are numerous cancer cachexia animal model as cancer itself, [41][42][43][44][45] for the other chronic diseases, the literature shows animal model of sepsis, 46 chronic obstructive pulmonary disease, 47 chronic renal failure, 48 and chronic heart failure. 46,[49][50][51][52] However, these animal models are inadequate to be used as a rheumatoid cachexia animal model.…”

Contemporary publication patterns in the Journal of Cachexia, Sarcopenia and Muscle by type and sub‐speciality: facts and numbers

“…For the first time, the journal was seeing Cochrane reviews of the evidence base for interventions in cachexia and related fields coming through. 27,28 There was growing evidence for the development of clinical trials and for improvements in clinical trial methodology by the development and validation of clinical screening tools 29 and scoring systems, 30 biomarkers, 31,32 and evaluative methodologies, including the establishment of normal ranges. [12][13][14][15][16][17] In the area of translational studies in the mechanisms of cachexia, studies were published on expression of spliced skeletal muscle genes, 18 along with scientific evaluations of skeletal muscle physiology, 19,20 growth, wasting, 21-23 preservation, 24,25 and regeneration.…”

“…26 Basic science approaches were also used to study the growing interest in the cardiac and cardio-metabolic effects of cancerrelated cachexia and of modern cancer therapies. 27,28 There was growing evidence for the development of clinical trials and for improvements in clinical trial methodology by the development and validation of clinical screening tools 29 and scoring systems, 30 biomarkers, 31,32 and evaluative methodologies, including the establishment of normal ranges. 33 These may help make trial design and novel treatment evaluation more precise in the future.The future pipeline of therapeutic interventions will be enhanced by the dissemination of basic reports into preclinical models [34][35][36][37] and early human trials 38 as a way of evaluating novel interventions.…”

Leucine and Its Importance for Cell Signalling Pathways in Cancer Cachexia-Induced Muscle Wasting

“…This is because cancer has significant effects on skeletal muscle, causing a catabolic state and resulting in widespread and progressive atrophy, including myocardial tissue. Studies have shown that cardiac atrophy can be a result of cancer evolution and its treatments [89][90][91]. These damages result in symptoms that can include breathlessness, lethargy, reduced exercise tolerance, congestive cardiac failure, and mortality [92].…”