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Effect of allopurinol and oxypurinol treatment on apoptosis in an experimental testicular torsion model
Emine Bilaloglu1, Levent Duman2, Yalcin Erzurumlu3, Onur Ertunc4, Yeliz Kart21Department of Pediatric Surgery, Bayburt State Hospital, Bayburt-Türkiye2Department of Pediatric Surgery, Suleyman Demirel University Faculty of Medicine, Isparta-Türkiye
3Department of Biochemistry, Suleyman Demirel University Faculty of Pharmacy, Isparta-Türkiye;4Department of Drug Research and Development, Institute of Health Sciences, Suleyman Demirel University, Isparta-Türkiye
4Department of Pathology, Gazi University Faculty of Medicine, Ankara-Türkiye
BACKGROUND: The aim of this study was to investigate whether allopurinol and oxypurinol treatment could mitigate oxidative stress and germ cell apoptosis in testicular ischemia-reperfusion (IR) injury.
METHODS: Thirty-two male rats were divided into four groups: Group 1 (Sham-Operated, n=8), in which the testicle was exposed but torsion was not performed; Group 2 (IR + Saline, n=8), in which torsion/detorsion was applied to the left testicle and 1 mL of normal saline was administered; Group 3 (IR + Allopurinol, n=8), in which torsion/detorsion was applied to the left testicle and 50 mg/kg allopurinol was administered; and Group 4 (IR + Oxypurinol, n=8), in which torsion/detorsion was applied to the left testicle and 50 mg/kg oxypurinol was administered. On postoperative day 28, left testicular tissue samples were collected, and total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were measured. Additionally, the gene expression levels of Bax, B-cell lymphoma 2 (Bcl-2), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor A (VEGF-A) were analyzed.
RESULTS: Allopurinol and oxypurinol significantly decreased OSI levels (p<0.001). Oxypurinol was found to be significantly more effective in reducing oxidative stress (p<0.001). Both allopurinol and oxypurinol significantly reduced Bax gene expression levels (p<0.001). Treatment with allopurinol (p=0.009) and oxypurinol (p=0.001) significantly increased Bcl-2 levels. Additionally, both agents significantly reduced the apoptosis index (p<0.001). Allopurinol (p1=0.007, p2<0.001) and oxypurinol (p1,2<0.001) treatments significantly increased eNOS and VEGF-A gene expression levels.
CONCLUSION: Allopurinol and oxypurinol reduce oxidative stress in the testis following IR injury, with oxypurinol demonstrating a greater antioxidant effect. Both treatments also reduce apoptosis by contributing positively to the eNOS and VEGF-A-mediated repair processes. Therefore, allopurinol and oxypurinol may serve as potential therapeutic agents for clinical application in testicular torsion.
Keywords: Testicular torsion, ischemia, reperfusion, allopurinol, oxypurinol
Deneysel testis torsiyonu modelinde allopurinol ve oksipurinol tedavisinin apoptozis üzerine etkisi
Emine Bilaloglu1, Levent Duman2, Yalcin Erzurumlu3, Onur Ertunc4, Yeliz Kart21Bayburt Devlet Hastanesi, Çocuk Cerrahisi Kliniği, Bayburt2Süleyman Demirel Üniversitesi, Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı, Isparta
3Süleyman Demirel Üniversitesi, Eczacılık Fakültesi, Biyokimya Anabilim Dalı, Isparta
4Gazi Üniversitesi, Tıp Fakültesi, Patoloji Anabilim Dalı, Ankara
AMAÇ: Allopurinol ve oksipurinol tedavisinin testis iskemi-reperfüzyonunda (IR) oksidatif stresi ve germ hücre apoptozunu azaltıp azaltamayacağını incelemek.
GEREÇ VE YÖNTEM: Otuz iki erkek sıçan dört gruba ayrıldı: Grup 1 (Sham-Ameliyat, n=8), testis açığa çıkarıldı, ancak torsiyon uygulanmadı; Grup-2 (IR+Salin, n=8), sol testise torsiyon/detorsiyon uygulandı ve 1 ml serum fizyolojik verildi; Grup-3 (IR+Allopurinol, n=8), sol testise torsi-yon/detorsiyon uygulandı ve 50 mg/kg allopurinol verildi; Grup 4 (IR+Oksipurinol, n=8), sol testise torsiyon/detorsiyon uygulandı ve 50 mg/kg oksipurinol verildi. Sol testis ameliyat sonrası 28. günde alındı ve dokuda TAS, TOS ve OSI düzeyleri ölçüldü. Ayrıca Bax, Bcl-2, eNOS ve VEGF-A gen ekspresyon düzeyleri incelendi.
BULGULAR: Allopurinol ve oksipurinol, OSI düzeylerini anlamlı şekilde azalttı (p<0.001). Oksipurinolün oksidatif stresi azaltmada anlamlı şekil-de daha etkili olduğu bulundu (p<0.001). Allopurinol ve oksipurinol, Bax gen ekspresyon düzeyini anlamlı şekilde azalttı (p<0.001). Allopurinol (p=0.009) ve oksipurinol (p=0.001) tedavisi Bcl-2 düzeyini anlamlı şekilde artırdı. Allopurinol ve oksipurinol apoptoz indeksini anlamlı şekilde azalttı (p<0.001). Allopurinol (p1=0.007, p2<0.001) ve oksipurinol (p1,2<0.001) tedavileri, eNOS ve VEGF-A gen ekspresyon seviyelerini anlamlı şekilde artırmıştır.
SONUÇ: Allopurinol ve oksipurinol, IR sonrası testiste oksidatif stresi azaltmada etkilidir ve oksipurinol daha güçlü bir antioksidan etkiye sahiptir. Allopurinol ve oksipurinol tedavisi, eNOS ve VEGF-A aracılı onarım sürecine olumlu katkıda bulunarak apoptozu azaltmada etkilidir. Bu açılardan, allopurinol ve oksipurinol, testis torsiyonunda klinik uygulamalar için potansiyel ajanlardır.
Anahtar Kelimeler: Testis torsiyonu, İskemi, reperfüzyon, Allopurinol, Oksipurinol
Manuscript Language: English