Cardiotoxic effects of chemotherapy treatment with doxorubicin and cyclophosphamide and the possible benefits of nutritional supplementation with leucine in pregnant Wistar rats with the Walker 256 tumor.

• Grant number: 23/01743-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2023
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Cristina Cintra Gomes Marcondes
• Grantee: Beatrice Candido Alves
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/02739-4 - Nutrition and cancer: study of molecular, proteomic and metabolomic aspects of experimental model of cachexia, AP.TEM

Abstract

Breast cancer is the most prevalent type of cancer during pregnancy. In such cases, neoadjuvant chemotherapy treatment is frequently used to halt tumour progression. This treatment involves the administration of doxorubicin and cyclophosphamide. Although these drugs are effective in treating cancer, they can lead to serious cardiotoxic side effects, which limit treatment and significantly contribute to long-term morbidity and mortality. Cachexia is a metabolic and nutritional syndrome that affects around 40% of breast cancer patients. Its symptoms include weight loss, fatigue, and loss of appetite. One strategy to reduce muscle mass loss and increase survival is to supplement the diet with leucine, an amino acid that promotes protein synthesis and slows protein degradation. Therefore, this project aims to conduct a preclinical study to investigate the effects of chemotherapy treatment on the morphology, morphometry, and cardiovascular parameters of pregnant Wistar rats with the Walker 256 tumour. Additionally, the project will evaluate whether a leucine-rich diet modulates the changes observed in the cardiac tissue of these animals. Pregnant adult Wistar rats will be distributed into six groups: 1- control animals; 2- Walker 256 tumour-bearing group; 3- Walker 256 tumour- bearing + doxorubicin and cyclophosphamide treatment; 4- animals fed a leucine-rich diet; 5- Walker 256 tumour-bearing + fed a leucine-rich diet; 6- Walker 256 tumour-bearing + doxorubicin and cyclophosphamide treatment + fed leucine-rich diet. The tumour will be implanted into the right flank SC in groups 2, 3, 5 and 6, and all animals will be evaluated during the 20-21 days of pregnancy, and then euthanised for collecting tissue and serum samples. Prior to euthanasia, the electrocardiogram analysis and blood pressure will be measured in all animals. Multiple groups comparison using ANOVA will be performed, following the Bonferroni test to detect significant differences between groups.