Montelukast prevents testes against ischemia-reperfusion injury through suppression of iNOS expression.
OBJECTIVE
To elucidate the mechanism of a possible protective effect of montelukast against testicular ischemia/reperfusion (I/R) injury.


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.


CONCLUSIONS
Montelukast exerts protective effects against testicular I/R injury by inhibiting neutrophil activity, reversing the oxidative stress markers, decreasing iNOS activity and attenuating apoptosis.
Department of Urology, Bezmialem Vakif University Faculty of Medicine, İstanbul, Turkey.
Mesrur Selçuk
MS
Sılay
Department of Pharmacology, Marmara University School of Pharmacy, İstanbul, Turkey.
Hale
H
Toklu
Department of Pathology, Şişli Etfal Training and Research Hospital, İstanbul, Turkey.
Ayşim
A
Özağarı
Department of Urology, Şişli Etfal Training and Research Hospital, İstanbul, Turkey.
Mustafa
M
Aydın
Department of Biochemistry, Marmara University Faculty of Medicine, İstanbul, Turkey.
Şermin
Ş
Tetik
Department of Pharmacology, Marmara University School of Pharmacy, İstanbul, Turkey.
Göksel
G
Şener
Department of Urology, Şişli Etfal Training and Research Hospital, İstanbul, Turkey.
Cengiz
C
Miroğlu
Department of Urology, Şişli Etfal Training and Research Hospital, İstanbul, Turkey.
Muammer
M
Kendirci
Ischemia; montelukast; reperfusion; testis; torsion