Protective effects of lithium against testicular ischemia-reperfusion injury: Involvement of the Akt/GSK-3β pathway

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 degrees 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-3(3 (GSK-3(3) 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-a, and nitric oxide metabolite levels by 44%, 78 %, 55 %, and 65 % compared to the vehicle group, respectively. It also inhibited GSK-3(3 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 ischemiareperfusion injury following surgical correction of testicular torsion.