Liraglutide Pretreatment Does Not Improve Acute Doxorubicin-Induced Cardiotoxicity in Rats

Area of Science:

• Cardiology
• Pharmacology
• Toxicology

Background:

• Doxorubicin is a vital chemotherapy agent, but its clinical utility is hampered by dose-limiting cardiotoxicity.
• The pathophysiology of doxorubicin-induced cardiotoxicity is complex and multifactorial.
• Glucagon-like peptide-1 (GLP-1) analogues show potential in mitigating oxidative stress and inflammation.

Purpose of the Study:

• To investigate the efficacy of liraglutide, a GLP-1 analogue, as a pretreatment to prevent doxorubicin-induced acute cardiotoxicity.
• To analyze the impact of liraglutide on cardiac function and molecular markers following doxorubicin administration in a rat model.

Main Methods:

• Sixty male Wistar rats were divided into four groups: Control, Doxorubicin, Liraglutide, and Doxorubicin + Liraglutide.
• Liraglutide or saline was administered for two weeks, followed by doxorubicin or saline injection.
• Cardiac function was assessed via echocardiography and isolated heart studies 48 hours post-doxorubicin administration.

Main Results:

• Doxorubicin administration led to significant impairment in systolic and diastolic cardiac function.
• Key molecular changes in doxorubicin-treated rats included increased myocardial catalase activity, higher TLR-4 and NFκB/p-NFκB ratio, and decreased Bcl-2 and p-NFκB.
• Liraglutide pretreatment did not improve cardiac function or alter the observed molecular changes, despite affecting food intake and body weight.

Conclusions:

• Doxorubicin-induced cardiotoxicity involves increased catalase activity, altered NFκB signaling, and reduced Bcl-2 expression.
• Liraglutide failed to demonstrate a protective effect against acute doxorubicin cardiotoxicity in this experimental model.
• Further research is needed to explore alternative strategies for managing doxorubicin-related cardiac side effects.