A novel role of Nano selenium and sildenafil on streptozotocin-induced diabetic nephropathy in rats by modulation of inflammatory, oxidative, and apoptotic pathways

The present study aimed to investigate the effect of nano selenium, sildenafil, and their combination on inflammation, oxidative stress, and apoptosis in streptozotocin-induced diabetic nephropathy in rats. Herein, a new anti-inflammatory pathway for sildenafil as a high-mobility group box (HMGB1) inhibitor was proposed using the molecular docking technique. Rats were divided into 7 groups: normal control, control nano selenium, control sildenafil, control diabetic, diabetic+ nano selenium, diabetic+ sildenafil, diabetic+ nano selenium+ sildenafil. The effects of drugs were evaluated by measuring serum urea, creatinine, lactate dehydrogenase (LDH), levels of tumor necrosis factor-alpha (TNF-α), Interleukin 1 beta (IL-1β), HMGB1, receptor advanced glycation end product (RAGE), malondialdehyde (MDA), thioredoxin reductase (TrxR) by biochemical assays, nuclear factor-kappa b (NF-κB), toll-like receptor (TLR4) by immunohistochemistry, gene expressions of caspase 3 and monocyte chemoattractant protein (MCP-1) besides histopathological investigations of renal cells. Results showed beneficial effects of 8 weeks of treatment by nano selenium and sildenafil supported by improvement in kidney function, histopathological changes, and reduction in all of these parameters. These results supported molecular docking that indicated sildenafil had a high binding score and interactions with the HMGB1 receptor. The current study demonstrated a renoprotective effect of nano‑selenium and sildenafil by interfering at multiple pathways, especially the HMGB1/NF-κB signaling pathway. [Display omitted] •Diabetic nephropathy is the most common cause of end-stage renal disease.•Oxidative stress-induced by diabetes leads to nephrotoxicity through activation of inflammatory pathways and release of inflammatory cytokines.•Investigation of the inflammatory markers such as; HMGB1, TNF-α, NF-κB and IL1β in kidney tissue.•Assess the potential therapeutic role of Sildenafil against experimentally induced nephrotoxicity.•Assess the potential therapeutic role of Nano-selenium against experimentally induced nephrotoxicity.