Selenium and iron oxide nanoparticles mitigate doxorubicin-induced cardiomyopathy in rats via Nox1/p53 pathway inhibition

Abstract

Cardiovascular diseases, such as arrhythmia and cardiomyopathy, are leading causes of mortality worldwide. Cardiomyopathy is often triggered by oxidative stress. Objective The current study aims to investigate the therapeutic potential of selenium and iron oxide (FeO) nanoparticles, individually and in combination, in treating doxorubicin (DOX)-induced cardiomyopathy in rats. Method Cardiomyopathy was induced in Wistar rats, where selenium, FeO nanoparticles, or both were formulated and tested on the rat model. Key findings DOX administration revealed a significant elevation in cardiac enzymes: creatinine kinase (CK-MB) and troponin-1 (cTn-1), and elevation of oxidative stress markers, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and malondialdehyde (MDA), together with a reduction in superoxide dismutase (SOD) and glutathione peroxidase (GPx). A significant elevation in inflammatory markers, protein kinase C (PKC), nuclear factor-kappa B (NF-kB), and metalloproteinase-9 (MMP-9), was obvious after DOX administration in rats for induction of cardiomyopathy together with histopathological alterations. Selenium and FeO nanoparticles groups significantly improved oxidative stress, inflammation, and apoptosis compared with the DOX group. Combined selenium and FeO nanoparticle groups showed better results compared with the other treatment groups. Conclusion Selenium and FeO nanoparticles showed potential anti-oxidant, anti-inflammatory and anti-apoptotic effects in the treatment of DOX-induced cardiomyopathy in rats.