Effects of liraglutide on the energy metabolism of peripheral muscle of rats treated acutely with doxorubicin

• Grant number: 24/14996-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2025
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Carolina Rodrigues Tonon
• Grantee: Eduarda Henriques Brito
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Doxorubicin is a chemotherapy drug used to treat several types of cancer, with high effectiveness, but can cause toxicity in several organs, limiting its use. Toxicity to peripheral muscles is multifactorial and not well stablished, but doxorubicin appears to alter muscle energy metabolism, leading to an increase in anaerobic metabolism. Loss of muscle mass is a prognostic marker in these patients, associated with worse quality of life and higher mortality. GLP-1 analogues are used in the treatment of diabetes and obesity and have improved muscle atrophy and strength in experimental studies. The objective of this study is to evaluate the effects of liraglutide on energy metabolism in acute myotoxicity induced by doxorubicin. For this, 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 group (C), doxorubicin (D), liraglutide (L) and doxorubicin + liraglutide (DL). Groups L and DL received a subcutaneous injection of liraglutide (GLP-1 analogue) 0.6mg/kg and groups C and D received an injection of saline daily for 14 days. After 12 days of treatment, groups D and DL received an intraperitoneal injection of doxorubicin 20 mg/kg, a single dose, and groups C and L received an injection of saline. After 48 hours, the animals were euthanized, the soleus and gastrocnemius muscles collected and stored at -80°C. The activities of enzymes involved in energy metabolism and protein expression of T troponin, CPK, DHL, PFK, GLUT4, CPT1 and OXPHOS will be evaluated by Western-Blot. Statistical analysis: 2-way ANOVA.