ANALYSIS OF OXIDATIVE CAPACITY IN CANCER CACHEXIA IN RATS SUBMITTED TO AEROBIC PHYSICAL TRAINING AND TREATED WITH METHOTREXATE CARRIER NANOPARTICLES

• Grant number: 24/14866-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Giovana Rampazzo Teixeira
• Grantee: Mateus Machado Frigo
• Host Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil

Abstract

Cancer cachexia is characterized by the involuntary loss of muscle mass during the cancerous state. It is estimated that 30% of deaths during cancer are caused directly by the effects of cachexia. The development of an alternative bionanotechnology for cancer treatment appears to be a promising treatment, allowing the delivery of chemotherapeutic agents in high doses, with low cytotoxicity. This treatment promotes the improvement of factors associated with cancer, increasing patient survival. When conjugated to lipid nanoemulsions (LDE), chemotherapeutic agents increase their half-life, decreasing their degradation in the bloodstream. On the other hand, tumor cells increase their lipid uptake to supply rapid cell multiplication. Therefore, the use of lipid nanoemulsions carrying chemotherapeutic agents can increase tumor uptake of the drug, thus increasing its anti-proliferative effects. Physical exercise can increase the clearance of low-density lipoprotein (LDL) receptors. In order to increase the efficiency of the LDE nanoparticle carrying the drug, we will associate aerobic physical exercise, investigating the responses of cancer and treatments in skeletal striated muscle. Thus, the objective of the study is to verify the effects of treatment with LDE+methotrexate (MTX) and aerobic physical exercise during carcinogenic development and cancer cachexia in Sprague-Dawley rats. Cancer will be induced by the application of a single dose (65 mg/kg) of the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). The animals will receive six doses of LDE-MTX (1 mg/kg) and the aerobic physical training protocol will last eight weeks. After the end of the experimental design, the animals will be euthanized and the soleus muscle will be collected for histological, histochemical, biochemical and molecular analyses.