Effect of montelukast on spinal cord ischemia/reperfusion injury

Abstract

AIm: Paraplegia due to ischemia-reperfusion (I/R) injury of the spinal cord is a devastating complication of thoracoabdominal aortic surgery. Cysteinyl leukotrienes are potent mediators of inflammation that are associated with I/R injury. The present study was designed to investigate the role of montelukast, a selective reversible CysLT1 receptor antagonist, on spinal cord I/R injury in an experimental model. mAterIAl and methOds: Twenty-one male Sprague-Dawley rats were randomly assigned to three groups (n=7 per group) as G1 (no aortic occlusion and montelukast administration), G2 (45 min. aortic occlusion; no montelukast administration) and G3 (45 min. aortic occlusion, 10 mg/kg montelukast administration). After neurologic evaluation using the Motor Deficit Index (MDI) score at the 48th hour of reperfusion, lumbar spinal cords were removed for histopathological evaluation and immunohistochemical staining for HSP70, interleukin-6 and myeloperoxidase (MPO).results: All rats in the G1 group had a normal neurological status and their MDI score was 0 (p<0.05). The MDI score of G3 was significantly lower than G2 group (2.8 vs. 5.5; p<0.05). Vacuolar congestion was found to be significantly lower in G1 than the other groups (p=0.0001). The interleukin-6 receptor level was found to be significantly lower in G3 group than the control group (p=0.013). There was no statistically significant difference found among the groups in terms of the degree of HSP70 and MPO staining.COnClusIOn: Increased generation of leukotrienes in postischemic organs play an important role in I/R injury. The findings of the current study demonstrated that montelukast improved motor recovery and decreased IL-6 levels in spinal cord I/R injury. KeywOrds:Spinal cord ischemia, Montelukast, Reperfusion injury, Rat, Experimental, CysLT1 receptor ÖZ AmAÇ: Çalışma, deneysel bir modelde, seçici tersinir bir CysLT1 reseptör antagonisti olan montelukastın, spinal kord iskemi-reperfüzyon (I/R) hasarı üzerindeki rolünü incelemek için tasarlandı. yÖntem ve GereÇler: Yirmi bir erkek Sprague-Dawley tipi sıçan, rasgele üç gruba (her grupta n = 7) ayrıldı; G1 (aort oklüzyonu ve montelukast uygulaması yok), G2 (45 dakika aort oklüzyonu; montelukast uygulaması yok) ve G3 (45 dk aort oklüzyonu, 10 mg / kg montelukast uygulaması). Reperfüzyonun 48. saatindeki Motor Defisit Indeksi (MID) skorlaması kullanılarak yapılan nörolojik değerlendirmeden sonra, lomber spinal kordlar, histopatolojik değerlendirme ve HSP70, interlökin-6 ve miyeloperoksidaz (MPO) için immünhistokimyasal boyama amacıyla çıkartıldı.BulGulAr: G1 grubundaki tüm sıçanların nörolojik durumu normaldi ve MDI skorları 0\'dı (p <0.05). G3\'ün MDI skoru, G2 grubuna göre anlamlı derecede düşük bulundu (2.8 vs 5.5; p <0.05 ). G1'de vaküoler konjesyon, diğer gruplara göre anlamlı derecede düşük bulundu (p = 0.0001). İnterlökin-6 reseptörü düzeyi, G3 grubunda kontrol grubuna göre istatistiksel olarak anlamlı düzeyde daha düşük bulundu (p = 0.013). HSP70 ve MPO boyanma derecesi açısından gruplar arasınd...

Effects of carvacrol administration on motor function following spinal ischemia and reperfusion

“…Motor deficit index data evaluations suggested that administering CAR 48 h after an injury reduced motor function capacity (MFC). Many studies in the literature showed that MFC was an important parameter for the evaluation of SIR (Badem et al, 2014;Erkut and Onk, 2015;Korkmaz et al, 2015;Liang et al, 2011). Some studies used motor function evaluation methods similar to those used in the current study (Ryu et al, 2018).…”

“…In Korkmaz et al (2015),which investigatedthe effects of CysLT1 receptor antagonist montelukast following SIR, MDI was evaluated for MFC scoring. In other studies, MFC scoring following SIR was performed by Tarlov scale (Erkut and Onk, 2015;Guven et al,2015) or Basso, Beattie, and Bresnahan (BBB) scoring (Basso et al, 1995;, which uses 21-point scoring to determine the activity of an animal.…”

“…), age, and patient-related factors. The range of occurrence is between 2.9% and 38% (Badem et al, 2014;Korkmaz et al, 2015). Decreasing ischemic times, reducing spinal cord swelling, and diminishing postoperative monitoring of neurological functions are some of the clinical applications for spinal ischemia prevention.…”

“…Moreover, the increased production of free radicals also causes an altered blood flow that has adverse clinical impacts (Bedreaget al, 2014;Crimi et al, 2012;Kayacan et al, 2019). There are many in vivo and in vitro studies examining improvementin loss of neurological function and attempts to reduce oxidative stress following SIR (Badem et al, 2014;Cemil et al, 2016;Erkut and Onk, 2015;Gokce et al, 2016a;Gökce et al, 2016b;Korkmaz et al, 2015;Liang et al, 2011;Shaafi et al,2011;Usulet al, 2008;Tokmak et al, 2015). However, no studies have examined the effects of carvacrol on SIR.…”

Montelukast promotes mitochondrial biogenesis via CREB/PGC-1α in human bronchial epithelial cells

“…Montelukast has displayed antioxidant and anti-inflammatory effects in various diseases. Montelukast has been shown to improve motor recovery and reduce IL-6 levels in spinal cord ischemia-reperfusion (I/R) injury [6]. Another study demonstrated that administration of montelukast decreased respiratory syncytial virus-induced mucus hyperproduction in a rodent in vivo model [7].…”