The protective effect of pregabalin and xanthenone on testicular ischemia/reperfusion injury in rats

• Published in: Fundamental & clinical pharmacology 2024-12, Vol.38 (6), p.1080-1093
• Main Authors: Abdel‐Fattah, Maha M., Ahmed, Ahmed Mamdouh, Saleh, Rabeh Khairy, Messiha, Basim Anwar Shehata, Rofaeil, Remon Roshdy
• Format: Article
• Language: English
• Subjects: ACE2; Angiotensin; Ang‐II/Ang‐(1–7); Animals; Antioxidants - pharmacology; Caspase; Cholesterol; Glutathione; Heme oxygenase (decyclizing); Injury prevention; Ischemia; Male; Nitric oxide; Oxidative Stress - drug effects; pregabalin; Pregabalin - pharmacology; Rats; Rats, Wistar; Reperfusion; Reperfusion Injury - drug therapy; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Spermatic cord; Spermatic Cord Torsion - complications; Spermatic Cord Torsion - drug therapy; Superoxide dismutase; T/D injury; Testes; testicular IR injury; Testis - drug effects; Testis - metabolism; Testis - pathology; Testosterone; Testosterone - blood; Tumor necrosis factor; Tumor necrosis factor-TNF; xanthenone
• ISSN: 0767-3981; 1472-8206; 1472-8206
• DOI: 10.1111/fcp.13027

Background Torsion of the spermatic cord is a hazardous and common urologic issue. The current work evaluates the possible protective effect of pregabalin (PGB) and xanthenone (XAN) in testicular ischemia/reperfusion injury induced by testicular torsion/detorsion in rats. Materials and methods Seven groups of adult male Wistar albino rats were allocated randomly into seven groups, namely, sham control, torsion/detorsion (T/D), PGB 50 mg/kg, PGB 100 mg/kg, XAN 1 mg/kg, XAN 2 mg/kg, and PGB 50 mg/kg plus XAN 1 mg/kg groups. Serum cholesterol and testosterone levels were determined. Also, the levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), superoxide dismutase (SOD), tumor necrosis factor‐α (TNF‐α), nuclear factor kappa B (NF‐қB), angiotensin (Ang) II, Ang‐(1–7), and angiotensin‐converting enzyme2 (ACE2) were assessed in testicular tissue. Immunohistochemical analysis of heme oxygenase‐1 (HO‐1) and caspase‐3 was performed. Finally, the histopathological examination of the testicular tissues was performed. Results The PGB 50 mg/kg, PGB 100 mg/kg, XAN 1 mg/kg, XAN 2 mg/kg, and PGB 50 mg/kg plus XAN 1 mg/kg groups showed a significant decrease in serum cholesterol, MDA, NO, TNF‐α, NF‐қB, and Ang‐II levels coupled with a significant increase in both testosterone and ACE2 expression. Furthermore, all test groups showed a significant improvement in the histopathological picture with a reduction in caspase‐3 and an increase in HO‐1 immunoexpression in testicular tissue. Conclusion PGB and XAN may have promising effects on preventing testicular T/D injury through antioxidant, anti‐inflammatory, and antiapoptotic actions.