Influence of GLP-1 analogue on intestinal microbiota and attenuation of doxorubicin-induced cardiotoxicity in rats
Description: Doxorubicin is an effective chemotherapy used for decades in the treatment of solid and hematologic malignancies. However, its cardiotoxicity represents the most severe side effect, limiting treatment and worsening patients' quality of life. There is not a highly effective treatment to prevent cardiotoxicity. Recently, changes in gut microbiota have been related to increased risk of cardiovascular diseases and doxorubicin could induce changes in diversity and quality of microbiota. Thus, drugs that modulate gut microbiota may be a potential strategy to prevent doxorubicin-induced cardiotoxicity. GLP-1 analogs have been shown to reduce oxidative stress and inflammation and have intestinal-trophic effects. Therefore, the study aims to evaluate the role of liraglutide, a GLP-1 analog, in attenuating acute doxorubicin-induced cardiotoxicity in rats through its activity in the gut microbiota. For this, we will use 60 male Wistar rats, which will be allocated in 4 groups: Control (C), Doxorubicin (D), Liraglutide (L), and Doxorubicin + Liraglutide (DL). The animals in groups L and DL will receive subcutaneous injection of 0.6 mg/kg liraglutide daily and groups C and D will receive saline, for 2 weeks. At the end of this period, the animals in groups D and DL will receive an intraperitoneal injection of doxorubicin 20 mg/kg once. After 48 hours of the dose of doxorubicin, the animals will be submitted to an echocardiogram, isolated heart study, and euthanasia to collect biological materials, which will be stored at -80 ° C. We will evaluate oxidative stress, heart and intestine's histology, ELISA for lipopolysaccharides, intestinal microbiota diversity and protein expression of troponin, NF-kB, TLR-2, ZO-1, Mucina-2, TNF-alpha in myocardium and colon by Western blot. Statistical analysis: 2-way ANOVA and significance adopted will be 5%. (AU)
Funding type: grant
Funder scheme: Auxílio à Pesquisa - Regular
Start date: 2023-04-01
End date: 2025-03-31
Investigator: Sergio Alberto Rupp de Paiva
Institution: Universidade Estadual Paulista (UNESP). Campus de Botucatu. Faculdade de Medicina (FMB)
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Funded outputs count: 4
Funder award ID: 22/15954-9
OpenAlex ID: G4366911350