Background: Schistosomiasis, a debilitating parasitic disease that affects millions worldwide, causes significant organ damage, with the kidneys being particularly vulnerable due to oxidative stress. Traditional treatment with praziquantel (PZQ) has limited efficacy in reversing renal injury. The present study investigated the therapeutic potential of combining resveratrol (RSV) and selenium nanoparticles (SeNp) to mitigate oxidative stress and inflammation in the renal tissue of Schistosoma mansoni (S. mansoni)-infected mice. The aim was to assess the effectiveness of RSV and SeNp, both separately and in combination, in counteracting S. mansoni induced renal injury through the novel biomarker monocyte chemoattractant protein- 1 (MCP-1). Methods: In a six-group in vivo assay design, RSV and SeNp were administered to S. mansoni-infected mice. Post-treatment, Renal functions parameters including: proteinuria, serum creatinine, nitrate/ nitrite, urine specific gravity, and urine PH were measured. key oxidative stress parameters including glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and MCP-1 mRNA expression folds were evaluated using quantitative real-time PCR. Histopathological changes by using Hematoxylin and Eosin (H&E) stain were assessed. Results: Non-infected, untreated control mice displayed baseline levels of renal functions, oxidative stress parameters (GSH, SOD, MDA and MCP-1 mRNA expression) and normal renal histology. In contrast, infection with S. mansoni significantly elevated MCP-1 mRNA expression and disrupted other oxidative stress and renal functions parameters, indicating enhanced oxidative stress and renal injury. Post-treatment with SeNp and RSV, both individually and in combination, notably reversed these effects. The combination therapy was particularly effective, demonstrating a substantial reduction in MCP-1 mRNA expression, normalization of other oxidative stress and renal functions markers. Histopathological analysis confirmed significant restoration of renal architecture and reduction of injury, suggesting robust protection against oxidative stress induced by the infection. Conclusion: The combination of SeNp and RSV presents a promising therapeutic strategy against schistosomiasis-renal injury, surpassing the effects of PZQ and single-agent treatments. These findings advocate for further exploration of combination therapy to improve outcomes in schistosomiasis management, highlighting the role of oxidative stress mitigation in combatting parasitic diseases.

Schistosoma mansoni; Renal Injury; Resveratrol; Selenium Nanoparticles; monocyte chemoattractant protein- 1.