Protective Effects of a Novel Agonist of Galanin Receptors Against Doxorubicin-Induced Cardiotoxicity in Rats

Area of Science:

• Cardiology
• Pharmacology
• Biochemistry

Background:

• Doxorubicin (DOX) is an effective antineoplastic agent, but its clinical use is limited by cardiotoxicity.
• Galanine ([βAla14, His15]-galanine (2-15), G) is a novel synthetic galanin receptor agonist with demonstrated cardioprotective effects in preclinical models.
• DOX-induced cardiotoxicity remains a significant clinical challenge, necessitating the development of effective cardioprotective strategies.

Purpose of the Study:

• To investigate the efficacy of galanine peptide G in mitigating doxorubicin-induced cardiotoxicity.
• To evaluate the impact of G on cardiac function, oxidative stress, and energy metabolism in a rat model of DOX cardiotoxicity.

Main Methods:

• Wistar rats were assigned to four groups: doxorubicin (DOX), DOX + G, G, and control (saline).
• Cardiac function was assessed via echocardiography; plasma thiobarbituric acid reactive substances (TBARS) and creatine kinase-MB (CK-MB) were measured.
• Myocardial energy metabolites (ATP, PCr) and mitochondrial respiration were analyzed in cardiac tissue.

Main Results:

• DOX treatment led to cardiac failure, reduced weight gain, increased plasma TBARS and CK-MB, depleted myocardial high-energy phosphates, and impaired mitochondrial respiration.
• Co-administration of G with DOX significantly reduced plasma TBARS, prevented CK-MB elevation, and preserved myocardial ATP, PCr, and mitochondrial respiratory function.
• Peptide G treatment improved left ventricular function parameters and promoted weight gain in DOX-treated rats.

Conclusions:

• Galanine peptide G effectively attenuates doxorubicin-induced cardiotoxicity in a preclinical setting.
• G demonstrates potential as a cardioprotective agent to mitigate the adverse cardiac effects of doxorubicin chemotherapy.
• Further research into G's mechanism of action and clinical application is warranted.