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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
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Authors Affiliations
  1. 1. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. School of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  4. 4. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Pathology, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

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