Mesrur Selçuk Sılay1, Hale Toklu2, Ayşim Özağarı3, Mustafa Aydın4, Şermin Tetik5, Göksel Şener2, Cengiz Miroğlu4, Muammer Kendirci4. 1. Department of Urology, Bezmialem Vakif University Faculty of Medicine, İstanbul, Turkey. 2. Department of Pharmacology, Marmara University School of Pharmacy, İstanbul, Turkey. 3. Department of Pathology, Şişli Etfal Training and Research Hospital, İstanbul, Turkey. 4. Department of Urology, Şişli Etfal Training and Research Hospital, İstanbul, Turkey. 5. Department of Biochemistry, Marmara University Faculty of Medicine, İstanbul, Turkey.
Abstract
OBJECTIVE: To elucidate the mechanism of a possible protective effect of montelukast against testicular ischemia/reperfusion (I/R) injury. MATERIAL AND METHODS: Fifty-one adult male Wistar-Albino rats were randomly assigned into 6 groups; sham + saline (S), sham + montelukast (M), I/R + S, I/R + S 30', I/R + M and I/R + M 30'. Saline or montelukast (10 mg/kg) was intraperitoneally administered 30 minutes prior to (S 30', M 30') and during detorsion (I/R + S, I/R + M) in the I/R groups. The I/R groups underwent 2 hours of ischemia followed by 4 hours (early-term) of reperfusion in unilateral testes. Half of the rats underwent 24 hours (late-term) of reperfusion to investigate long-term effects. Testicular tissue samples were examined for biochemical and histopathological parameters. Germ cell apoptosis was evaluated using apoptosis-activating factor 1 (Apaf-1). Inducible nitric oxide synthase (iNOS) activity was analyzed in late-term reperfusion groups. Spermatogenic functions were assessed for each testis based on the Johnsen criteria. RESULTS: Unilateral I/R caused a significant increase in serum TNF-α levels in the early-term group compared to the sham groups. Malondialdehyde levels and myeloperoxidase activity were found to be elevated in the I/R groups and accompanied with a significant decrease in glutathione levels when compared to the sham groups. I/R significantly increased iNOS activity and germ cell apoptosis compared to the sham groups. Montelukast treatment significantly reversed all of these parameters and achieved comparable results with the sham groups. Finally, spermatogenic indices were similar for the bilateral testes between all groups. CONCLUSION: Montelukast exerts protective effects against testicular I/R injury by inhibiting neutrophil activity, reversing the oxidative stress markers, decreasing iNOS activity and attenuating apoptosis.
OBJECTIVE: To elucidate the mechanism of a possible protective effect of montelukast against testicular ischemia/reperfusion (I/R) injury. MATERIAL AND METHODS: Fifty-one adult male Wistar-Albino rats were randomly assigned into 6 groups; sham + saline (S), sham + montelukast (M), I/R + S, I/R + S 30', I/R + M and I/R + M 30'. Saline or montelukast (10 mg/kg) was intraperitoneally administered 30 minutes prior to (S 30', M 30') and during detorsion (I/R + S, I/R + M) in the I/R groups. The I/R groups underwent 2 hours of ischemia followed by 4 hours (early-term) of reperfusion in unilateral testes. Half of the rats underwent 24 hours (late-term) of reperfusion to investigate long-term effects. Testicular tissue samples were examined for biochemical and histopathological parameters. Germ cell apoptosis was evaluated using apoptosis-activating factor 1 (Apaf-1). Inducible nitric oxide synthase (iNOS) activity was analyzed in late-term reperfusion groups. Spermatogenic functions were assessed for each testis based on the Johnsen criteria. RESULTS: Unilateral I/R caused a significant increase in serum TNF-α levels in the early-term group compared to the sham groups. Malondialdehyde levels and myeloperoxidase activity were found to be elevated in the I/R groups and accompanied with a significant decrease in glutathione levels when compared to the sham groups. I/R significantly increased iNOS activity and germ cell apoptosis compared to the sham groups. Montelukast treatment significantly reversed all of these parameters and achieved comparable results with the sham groups. Finally, spermatogenic indices were similar for the bilateral testes between all groups. CONCLUSION:Montelukast exerts protective effects against testicular I/R injury by inhibiting neutrophil activity, reversing the oxidative stress markers, decreasing iNOS activity and attenuating apoptosis.
Authors: Jorge G Mogilner; Michael Lurie; Arnold G Coran; Ofer Nativ; Eitan Shiloni; Igor Sukhotnik Journal: Pediatr Surg Int Date: 2006-01 Impact factor: 1.827