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Protective Effects of Lithium Against Testicular Ischemia-Reperfusion Injury: Involvement of the Akt/Gsk-3Β Pathway Publisher Pubmed



Ghasemi M1, 2 ; Basiri A3 ; Mohammad Jafari R4, 5 ; Shafaroodi H4, 5 ; Tavangar SM6 ; Mohammadi Hamaneh A5 ; Dehpour AR2, 4, 5
Authors

Source: Journal of Pediatric Urology Published:2025


Abstract

Background: Testicular torsion is a urological emergency requiring timely intervention to prevent irreversible damage, infertility, or orchiectomy. Objective: To investigate the protective effects of lithium against testicular torsion/detorsion (T/D) damage in a rat model. Methods: Seventy-two adult rats were randomly assigned to six groups: Group I: sham-operated control; Group II: lithium treatment with sham surgery; Groups III-VI: 4-h ischemia by 720° counterclockwise testis twisting, followed by 24-h reperfusion. Two hours before the onset of reperfusion, rats in Groups III-VI received vehicle or varying doses of lithium chloride (12, 30, or 60 mg/kg). We assessed oxidative stress, inflammation, and nitrosative stress biomarkers, glycogen synthase kinase-3β (GSK-3β) levels, and conducted histopathological examinations. Results: Lithium showed remarkable protective effects against T/D injury, with 60 mg/kg being most effective. This dosage significantly reduced malondialdehyde, interleukin-6, tumor necrosis factor-α, and nitric oxide metabolite levels by 44 %, 78 %, 55 %, and 65 % compared to the vehicle group, respectively. It also inhibited GSK-3β by promoting Ser9 phosphorylation. Histopathological analysis revealed lithium treatment was effective in minimizing testicular damage, restoring testicular weight, and preserving the structural integrity of seminiferous tubules. Conclusion: Despite previous reports of lithium toxicity in testicular tissue, lithium treatment serves as a promising option to prolong the therapeutic window for intervention and protect against ischemia-reperfusion injury following surgical correction of testicular torsion. © 2025 Journal of Pediatric Urology Company
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