Sophocarpine Alleviates Testicular Ischemia-Reperfusion Injury by Modulating Ferroptosis via the AKT Pathway in Rats.

Abstract

BACKGROUND: Testicular torsion is a common urological emergency that can lead to irreversible spermatogenic dysfunction and infertility. Sophocarpine, derived from Sophora flavescens Ait, has demonstrated broad therapeutic effects, including protection against ischemia-reperfusion injury (IRI). However, its effects on testicular IRI remain underexplored. OBJECTIVE: This study aimed to assess the protective effects of sophocarpine on bilateral testes in a rat model and to investigate the underlying mechanisms involved. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly assigned to five groups: the sham, control, sophocarpine, control + wortmannin, and sophocarpine + wortmannin groups (n = 7 rats per group). All groups, except for the sham group, underwent unilateral testicular IRI. The procedure involved 3 h of right spermatic cord torsion (720° clockwise) followed by 3 h of detorsion. Sophocarpine (administered at a dose of 30 mg/kg) was given to the rats in the respective treatment groups. The therapeutic effects were evaluated via histological analysis, oxidative stress assessment, inflammatory response measurement, protein analysis, and immunohistochemistry. RESULTS: Sophocarpine treatment significantly protected the bilateral testes after unilateral testicular torsion-detorsion, as indicated by a reduction in the testis weight-to-body weight (TW/BW) ratio, testicular volume, and structural damage. Additionally, sophocarpine increased the seminiferous tubule diameter and epithelial height. The treatment also suppressed oxidative stress and inflammatory responses. Notably, sophocarpine inhibited ferroptosis through the AKT signaling pathway, as evidenced by increased phosphorylation of AKT in the testes. Furthermore, the AKT inhibitor wortmannin reversed both the phosphorylation of AKT and the protective effects of sophocarpine on the testes. DISCUSSION AND CONCLUSION: Sophocarpine effectively protects the bilateral testes after unilateral testicular torsion-detorsion, with protective effects through ferroptosis mediated by the AKT signaling pathway, highlighting its potential as a therapeutic target in testicular IRI.