Heart World Conference 2026

Abstract

Background:

Doxorubicin (DOX) is an effective chemotherapeutic agent whose clinical utility is limited by cumulative cardiotoxicity involving oxidative stress, mitochondrial dysfunction, inflammation, and cardiomyocyte death. Theaflavin-3,3′-digallate (TFDG) possesses antioxidant and cytoprotective properties, while β-chitosan-based nanodelivery may enhance its therapeutic performance. This study evaluated the cardioprotective potential of TFDG and zinc co-loaded β-chitosan nanoparticles against DOX-induced cardiac injury in rats.

Methods:

A 21-day experimental rat model of DOX-induced cardiotoxicity was employed. Animals were assigned to normal control, DOX control, blank β-chitosan nanoparticles, free TFDG, zinc salt, TFDG-loaded β-chitosan nanoparticles, zinc-loaded β-chitosan nanoparticles, TFDG + zinc physical mixture, and TFDG + zinc co-loaded β-chitosan nanoparticle groups. Body weight and cardiac morphology were evaluated. Serum LDH, CK-MB, AST, and cardiac troponin-I were assessed as markers of myocardial injury. Cardiac histopathology and qRT-PCR analysis of selected inflammatory, antioxidant, mitochondrial, and apoptosis-associated genes were also performed.

Results:

DOX exposure produced progressive body-weight loss, elevated cardiac injury biomarkers, myocardial structural alterations, and dysregulation of cardiotoxicity-associated genes. Treatment groups demonstrated varying degrees of protection, with the TFDG + zinc co-loaded β-chitosan nanoparticle formulation showing the greatest overall protective response. The formulation attenuated biochemical alterations, preserved myocardial architecture, and favorably modulated molecular markers associated with oxidative stress, mitochondrial homeostasis, inflammation, and apoptosis.

Conclusion:

TFDG and zinc co-loaded β-chitosan nanoparticles demonstrated promising cardioprotective activity against DOX-induced cardiac injury. The findings support further investigation of this nanoformulation as a potential adjunct strategy for limiting anthracycline-associated cardiotoxicity.