Ashraf Mohamed Sadek, Basma H Amin, Zienab E Eldin, Heba R Hashem
Male reproductive impairment is rising globally. High-fructose consumption (HFD) is a major lifestyle contributor to testicular oxidative stress, inflammation, and impaired spermatogenesis. This study aimed to enhance the therapeutic potential of resveratrol (RES) by developing a cerium-based metal-organic framework encapsulating RES and coated with polyvinyl alcohol (Ce-BTC@RES-PVA) to evaluate its effect in a rat model of HFD-induced testicular dysfunction. The nanocarrier was synthesized and structurally characterized by DLS, XRD, FTIR, and SEM. Fifty-six rats were divided into control, HFD (60% fructose), HFD + free RES, HFD + Ce nanoparticles, and HFD + Ce-BTC@RES-PVA (5, 10, 20 mg/kg RES equivalent). After 8 weeks of treatment, samples were collected. Light microscopy and ultrastructural (TEM) examination with Johnsen score, sperm analysis, hormonal assay, oxidative stress markers (MDA, GSH, SOD), inflammatory cytokines (TNF-α, IL-6), and gene expression (Nrf2, Bax, Bcl2 by qPCR) were assessed. Microscopic examination of the HFD section revealed significant distortion in seminiferous tubules, shrunken spermatogenic and Leydig cells with pyknotic nuclei associated with reduced Johnsen score, GSH, SOD, and Nrf2 mRNA, and elevation of MDA, TNF-α, IL-6, and Bax/Bcl2 ratio. Ce-BTC@RES-PVA improved testicular morphology, enhanced antioxidant status, reduced inflammatory mediators, and restored the balance between pro and anti-apoptotic markers. The improvements were more pronounced than that with free RES, indicating superior therapeutic effect of the nanocarrier. Overall, Ce-BTC@RES-PVA improves RES efficacy in mitigating fructose-induced testicular dysfunction via coordinated antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, offering a promising strategy for metabolic syndrome-associated male reproductive impairment and support further investigation into its translational applicability.