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Fe-EGCG Nanozymes Ameliorate Erectile Dysfunction Induced by Cavernous Nerve Injury Through Inhibition of Oxidative
Zhiyue Wu1,2, Jiayin Hu3, Zhenbo Wang3
1Department of Urology, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
Background:
Cavernous nerve injury-induced erectile dysfunction (CNI-ED) is a common postoperative complication of pelvic surgery that currently lacks effective treatments. Oxidative stress (OS) plays a central role in its pathogenesis. Although epigallocatechin gallate (EGCG) has demonstrated antioxidant properties, its clinical application is limited by poor stability and bioavailability. Iron-EGCG nanozymes (Fe-EGCG), which integrate the enzymatic properties of nanoparticles with the antioxidant characteristics of EGCG through metal-polyphenol coordination, may provide a superior solution for restoring oxidative stress balance.
Objective:
To investigate the therapeutic effects and underlying mechanisms of Fe-EGCG in ameliorating CNI-ED.
Materials And Methods:
Fe-EGCG was synthesized via metal-polyphenol coordination and characterized for morphology and catalytic activity. Its reactive oxygen species (ROS) scavenging capacity was verified in vitro using PC-12 cells. Twenty-four rats were randomly assigned to four groups: sham-operated, bilateral cavernous nerve injury (BCNI), BCNI + EGCG, and BCNI + Fe-EGCG. EGCG and Fe-EGCG (100 µL, 2 mg/mL) were locally injected at the cavernous nerve injury site. Three weeks post-treatment, erectile function was evaluated. Cavernous nerves and penile tissues were collected for ultrastructural, histological, and molecular biological analyses.
Results:
Fe-EGCG nanozymes were successfully synthesized and characterized. In vitro experiments demonstrated that Fe-EGCG exhibited significantly stronger superoxide dismutase (SOD) and catalase (CAT) activities, as well as superior ROS scavenging capacity, compared to EGCG. In vivo studies further revealed that Fe-EGCG achieved better therapeutic outcomes than EGCG. Compared with the BCNI group, both EGCG and Fe-EGCG treatments significantly alleviated neural damage. This effect was evidenced by increased axonal density, enhanced Schwann cell proliferation, and restoration of neuronal nitric oxide synthase (nNOS) expression. Additionally, erectile function was significantly improved in both treatment groups. The BCNI rats exhibited decreased smooth muscle content, increased collagen deposition in the corpus cavernosum, and upregulated fibrosis markers, all of which were significantly attenuated following EGCG and Fe-EGCG administration. Mechanistically, both treatments reduced oxidative stress levels and were associated with upregulation of the Nrf2/HO-1 pathway and downregulation of NLRP3 inflammasome activity.
Discussion And Conclusion:
Fe-EGCG ameliorates CNI-ED by attenuating oxidative stress, protecting nerves, and inhibiting penile fibrosis. This study establishes Fe-EGCG as a novel and promising therapeutic strategy for CNI-ED. As a nanozyme self-assembled from metal ions and natural organic ligands, it enhances the efficacy of traditional antioxidants through synergistic effects.
