GLP-1 Receptor Agonist Exenatide Protects Against Doxorubicin-Induced Cardiotoxicity Through the SIRT1 Pathway: An Electrocardiographic, 99mTc-PYP Scintigraphic, and Biochemical Study.

Background and

Objectives

This study was designed to evaluate the potential cardioprotective effect of Exenatide against doxorubicin (DOX)-induced myocardial injury in rats by assessing scintigraphic alterations together with oxidative stress and inflammation. Materials and

Methods

This study included 28 adult male Wistar albino rats that were randomized to 4 groups (n = 7): control, Exenatide alone, DOX (receiving DOX (18 mg/kg, i.p) on days 5-7; Exenatide + DOX (treated with Exenatide together with the DOX). On day 8, ECG, 99mTc-PYP scintigraphy, and biochemical parameters were evaluated.

Results

DOX caused ECG abnormalities-bradycardia, significant QT prolongation, and elevated ST-segment amplitude-along with increased myocardial PYP uptake. Exenatide + DOX group significantly improved ECG changes. Biochemically, DOX markedly increased cardiac injury biomarkers (cTnT, CK, CK-MB), hepatic and renal injury markers (ALT, AST, LDH, BUN, creatinine), SIRT-1 level, inflammatory marker (NF-κB, TNF-α, IL-6, NO) and oxidative stress indicators (MDA, TOS), while decreasing antioxidant defenses (GSH, TAS, Nrf2). Exenatide co-treatment significantly attenuated all DOX-induced changes.

Conclusions

Exenatide markedly attenuates DOX-induced cardiotoxicity by improving electrical conduction, reducing myocardial radiotracer uptake, and restoring oxidative-inflammatory balance through partial recovery of the SIRT-1/Nrf2/NF-κB pathway.