Effects of liraglutide on collagen dynamics in doxorubicin-induced acute cardiotoxicity in rats

• Grant number: 24/14998-8
• 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: Maria Luisa Sousa Fonseca
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Doxorubicin is a widely used chemotherapy drug, but its use may be limited due to side effects, such as cardiotoxicity, which can lead to heart failure, a chronic and irreversible disease, with high morbidity and mortality rates. The activation of matrix metalloproteinases, which are enzymes responsible for the degradation of the extracellular matrix, appear to be involved in the pathophysiology of the disease. Liraglutide, a GLP-1 analogue, is a medication used to treat diabetes and obesity, which has shown some cardiovascular benefits. However, its effect on the regulation of the extracellular matrix has not yet been studied. The objective of this work is to evaluate the effect of liraglutide on collagen dynamics in acute cardiotoxicity induced by doxorubicin in rats. Fragments of the left ventricle collected from a previous project (CEUA-FMB 1400/2021) will be used, which used male Wistar rats allocated into 4 groups: control group (C), doxorubicin (D), liraglutide (L) and doxorubicin + liraglutide (DL). Animals in groups L and DL received a subcutaneous injection of 0.6mg/kg liraglutide and groups C and D received an injection of 0.9% saline daily for 14 days. After 12 days of treatment with liraglutide, animals in groups D and DL received an intraperitoneal injection of 20 mg/kg doxorubicin, a single dose, and groups C and L received an injection of 0.9% saline. After 48 hours of doxorubicin administration, the animals were euthanized, the heart tissue was collected and stored at -80°C. We will evaluate the activity of MMP-2 and -9 by zymography, protein expression of MMP-2, MMP-9, TIMP-1, TIMP-4, collagen I and III by Western-Blot and quantification of the interstitial collagen fraction in histology. Statistical analysis: 2-way ANOVA, with significance set at 5%.