Doxorubicin (DOX) is a potent anticancer drug with adverse cardiotoxic effects. Alginates are multifunctional biopolymers and polyelectrolytes derived from the cell walls of brown seaweeds. They are nontoxic, biocompatible, and biodegradable, and hence, utilized in several biomedical and pharmaceutical applications. Here, we investigated the potential cardioprotective effect of thermally treated sodium alginate (TTSA), which was extracted and purified from the seaweed Sargassum aquifolium, in treating acute DOX cardiotoxicity and apoptotic pathways in rats. UV-visible spectroscopy, Fourier-transform infrared, and nuclear magnetic resonance (1H-NMR) spectroscopy techniques were used to characterize TTSA. CK-MB and AST levels in sera samples were determined. The expression levels of Erk-2 (MAPK-1) and iNOS genes were investigated by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression levels of Erk-2, anti-apoptotic p53, and caspase-3 were analyzed using western blotting and ELISA. For the in vivo studies, sixty rats were randomly divided equally into six groups and treated with DOX, followed by TTSA. We revealed that treatment with TTSA, which has low molecular weight and enhanced antioxidant properties, improved DOX-mediated cardiac dysfunction and alleviated DOX-induced myocardial apoptosis. Furthermore, TTSA exhibited a cardioprotective effect against DOX-induced cardiac toxicity, indicated by the increased expression of MAPK-1 (Erk2) and iNOS genes, which are implicated in the adaptive responses regulating DOX-induced myocardial damage. Moreover, TTSA significantly (p < 0.05) suppressed caspase-3 and upregulated anti-apoptotic protein p53 expression. TTSA also rebalanced the cardiomyocyte redox potential by significantly (p < 0.05) increasing the levels of endogenous antioxidant enzymes, including catalase and superoxide dismutase. Our findings suggest that TTSA, particularly at a dose of 400 mg/kg b.w., is a potential prophylactic supplement for treating acute DOX-linked cardiotoxicity.
Keywords: Apoptosis; Brown seaweeds; Cardiotoxicity; Doxorubicin; MAPKs; Natural antioxidants; Oxidative stress; Sodium alginate.
© 2023. The Author(s).