Montelukast prevents testes against ischemia-reperfusion injury through suppression of iNOS expression

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.

Effect of etoricoxib on experimental oxidative testicular ischemia-reperfusion damage in rats induced with torsion-detorsion

“…This finding indicates that our experimental results are consistent with those in the literature. Aside from MDA, torsion-detorsion was reported to cause a significant increase in MPO activity in tissue [ 25 ]. I/R is a pathologic process that expands with inflammation [ 12 ].…”

The protective effect of montelukast against skeletal muscle ischaemia-reperfusion injury: an experimental rat model

“…Evaluation was made at ×40 microscope magnification and scoring was accepted as 0 = normal, 1 = mild effect, 2 = moderate effect, and 3 = severe effect (Table 1). [10] Biochemical Analyses…”

“…It has been reported that it protects the kidney and bladder from ischemia/reperfusion damage, and that this molecule is beneficial in ethanol-induced mucosa injury, multi-organ failure due to sepsis, colitis, and testis torsion. [5][6][7][8][9] In addition, the use of various pharmacological and immunological agents has been suggested to decrease or avoid reperfusion injury. However, there has been no appropriately designed study regarding the effect of Montelukast on tourniquet use models.…”

The effect of montelukast on depression behaviour in rat forced swimming test

“…alt grubu). Çalışma-mızda montelukast'ın uygulanan dozu daha önce yapılan çalışmalara dayanmaktadır (18,19). Diğer altgruplara ise montelukast yerine %0.9'luk SF, 100 µL/kg ile 10 günlük sü-re ile verildi.…”