Effects of liraglutide on the energy metabolism and atrophy pathways of peripheral muscle in rats treated acutely with doxorubicin

• Grant number: 24/20730-8
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2025
• End date: January 31, 2028
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Carolina Rodrigues Tonon
• Grantee: Carolina Rodrigues Tonon
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Bertha Furlan Polegato ; Mariana Janini Gomes ; Marina Politi Okoshi

Abstract

Doxorubicin is a chemotherapy drug used to treat several types of cancer, with high effectiveness; however, its toxicity in several organs may limit clinical use. Peripheral muscles toxicity is multifactorial and not well stablished, but doxorubicin appears to alter muscle energy metabolism, leading to increased anaerobic metabolism and muscle atrophy. Muscle mass loss is a prognostic marker in cancer patients, associated with impaired quality of life and increased mortality. The use of glucagon-like peptide (GLP-1) analogues in the treatment of diabetes and obesity has improved muscle atrophy and strength in experimental studies. The objective of this study is to evaluate the effects of liraglutide on energy metabolism and expression of proteins of atrophy signaling pathways in doxorubicin-induced acute myotoxicity. Fragments of the soleus and gastrocnemius muscles collected in a previous project (CEUA-FMB 1400/2021) will be used. We used male Wistar rats allocated into 4 groups: control (C), doxorubicin (D), liraglutide (L) and doxorubicin + liraglutide (DL). L and DL groups received a subcutaneous injection of liraglutide (a GLP-1 analogue) at the dose of 0.6 mg/kg; C and D groups received an injection of saline daily for 14 days. After 12 days, D and DL received a single intraperitoneal injection of doxorubicin 20 mg/kg; C and L groups received a saline injection. After 48 hours, the rats were euthanized and the soleus and gastrocnemius muscles collected and stored at -80 °C. The activity of enzymes involved in energy metabolism and protein expression of troponin T, CK, LDH, PFK, GLUT4, CPT1, OXPHOS, PCG1-¿, PPAR¿, OXPHOS, calpain-1, caspase 3, atrogin-1, MuRF-1, myogenin, IRS-1 and AKT will be evaluated by Western-blot and, TNF-¿, NF¿B, IL-6 and IL-10 by ELISA in the collected muscles. Statistical analysis will be performed using 2-way ANOVA. (AU)