Arab gum coating enhances the bioavailability and therapeutic potential of nanoselenium in cisplatin-induced testicular toxicity

Abstract

Abstract While Cisplatin remains a cornerstone of oncological intervention, its induction of systemic oxidative stress arranges a deleterious cascade that compromises male reproductive homeostasis. Selenium nanoparticles (SeNPs) may protect against oxidative stress and capping them with Arab gum (AG) could enhance their therapeutic efficacy. This study investigated the comparative gonadoprotective potential of Selenium Nanoparticles (SeNPs) and Arab gum (AG)-coated SeNPs (AG-SeNPs) against Cis-induced testicular dysfunction. Forty-five male Wistar rats were randomized into nine experimental groups: four baseline controls (Normal, AG, SeNPs, and AG- SeNPs) and five treatment groups receiving AG, SeNPs, AG-SeNPs, or a physical mixture of AG + SeNPs following Cis administration. Assessment parameters included the gonadosomatic index, biochemical markers of oxidative stress (CAT, GPX, MDA), and pro-inflammatory cytokines (TGF-beta, TNF-α and IL-6). Testicular integrity was further evaluated via histopathology, PCNA protein expression (cellular proliferation), and DNA fragmentation analysis using the Comet assay and apoptotic markers (Caspase-3 and Cytochrome C release). Administration of AG-SeNPs demonstrated superior gonadoprotective efficacy compared to uncoated SeNPs or physical mixtures. AG-SeNPs significantly restored redox homeostasis, via augmenting antioxidant enzyme activities (CAT, GPX) and reducing lipid peroxidation (MDA). Furthermore, AG-SeNPs significantly downregulated inflammatory signaling (TGF-beta, TNF-α and IL-6) and mitigated DNA damage. The treatment preserved genomic stability and inhibited the intrinsic apoptotic pathway by suppressing Cytochrome C release and Caspase-3 activation. Histological examination confirmed the restoration of seminiferous tubular architecture and enhanced cellular proliferation (PCNA expression). These findings suggest that AG-coating enhances the therapeutic index of SeNPs, likely due to improved bioavailability and synergistic antioxidant properties. AG-SeNPs represent a promising nanomedicine-based strategy for mitigating the gonadotoxic side effects of cisplatin-based chemotherapy.