Abozaid_2026_Immunopharmacol.Immunotoxicol__1

BACKGROUND: Doxorubicin is a potent anthracycline employed in the management of several malignant conditions. While it serves as an effective anticancer agent, its therapeutic application is constrained by dose-dependent cardiotoxicity. Galantamine is a reversible competitive antagonist of cholinesterase utilized in the management of Alzheimer's disease.Aim of the workThis work sought to ascertain the cardioprotective benefits of GALA versus cardiotoxicity triggered by DOX and elucidate the fundamental molecular pathways. MATERIALS AND METHODS: Rats were randomized to four groups, as follows: control, GALA (5 mg/kg, P.O.), DOX single dose (20 mg/kg, I.P), and DOX + GALA. RESULTS: Unlike the DOX group, GALA pretreatment mitigated cardiotoxicity, as revealed by a notable drop in serum CK-MB and CTnI, along with marked improvement in the histopathological features of heart tissues. GALA also diminished oxidative damage, as recognized by reduced MDA and elevated GSH and SOD. Moreover, GALA pretreatment reduced DOX-induced inflammation, as revealed by a decline in NF-kappaB, along with TNF-alpha and IL-6. Furthermore, GALA pretreatment mitigated DOX's apoptotic effects, as revealed by reduced Bax and caspase-3, alongside an elevation in Bcl-2 and its upstream signaling pathway PI3K/AKT. CONCLUSION: These findings indicated that GALA's protective impact versus DOX-induced cardiotoxicity is attributed to its capability to modulate PI3K/AKT, Bax/Bcl-2, and NF-kappaB/TNF-alpha pathways.