Doxorubicin is an effective drug for cancer treatment; however, cardiotoxicity limits its use. Cardiotoxicity pathophysiology is multifactorial. GLP-1 analogues have been shown to reduce oxidative stress and inflammation. In this study, we evaluated the effect of pretreatment with liraglutide on doxorubicin-induced acute cardiotoxicity. A total of 60 male Wistar rats were allocated into four groups: Control (C), Doxorubicin (D), Liraglutide (L), and Doxorubicin + Liraglutide (DL). L and DL received subcutaneous injection of liraglutide 0.6 mg/kg daily, while C and D received saline for 2 weeks. Afterwards, D and DL received a single intraperitoneal injection of doxorubicin 20 mg/kg; C and L received an injection of saline. Forty-eight hours after doxorubicin administration, the rats were subjected to echocardiogram, isolated heart functional study, and euthanasia. Liraglutide-treated rats ingested significantly less food and gained less body weight than animals that did not receive the drug. Rats lost weight after doxorubicin injection. At echocardiogram and isolated heart study, doxorubicin-treated rats had systolic and diastolic function impairment. Myocardial catalase activity was statistically higher in doxorubicin-treated rats. Myocardial protein expression of tumor necrosis factor alpha (TNF-α), phosphorylated nuclear factor-κB (p-NFκB), troponin T, and B-cell lymphoma 2 (Bcl-2) was significantly lower, and the total NFκB/p-NFκB ratio and TLR-4 higher in doxorubicin-treated rats. Myocardial expression of OPA-1, MFN-2, DRP-1, and topoisomerase 2β did not differ between groups (p > 0.05). In conclusion, doxorubicin-induced cardiotoxicity is accompanied by decreased Bcl-2 and phosphorylated NFκB and increased catalase activity and TLR-4 expression. Liraglutide failed to improve acute doxorubicin-induced cardiotoxicity in rats.

Doxorubicin is a widely used chemotherapy for the treatment of several types of cancer. However, its application is restricted due to adverse effects, particularly cardiotoxicity, which can progress to heart failure—a chronic and debilitating condition. Several mechanisms have been identified in the pathophysiology of doxorubicin-induced cardiotoxicity, including oxidative stress, mitochondrial dysfunction, inflammation, and disruption of collagen homeostasis. More recently, dysbiosis of the gut microbiota has been implicated in the development and perpetuation of cardiac injury. Studies have reported alterations in the composition and abundance of the microbiota during doxorubicin treatment. Therefore, as of recent, there is a new field of research in order to develop strategies involving the gut microbiota to prevent or attenuate cardiotoxicity since there is no effective therapy at the moment. This narrative review aims to provide an update on the role of gut microbiota and intestinal permeability in the pathophysiology of cardiovascular diseases, and more specifically doxorubicin-induced cardiotoxicity. Additionally, it seeks to establish a foundation for future research targeting gut microbiota to alleviate cardiotoxicity.