Hale TOKLU, Mustafa DENİZ, MERAL YÜKSEL, Meral KAYER-UYSAL, Göksel ŞENER

The protective effect of melatonin and amlodipine against cerebral ischemia/reperfusion-induced oxidative brain injury in rats

Amaç: Bu çalışmada melatonin ve amlodipinin iskemi/reperfüzyon (İ/R) ile oluşan beyin hasarına karşı olası koruyucu etkileri araştırıldı. Yöntem: Wistar Albino sıçanlar 15 dakika bilateral carotid arter oklüzyonunu takiben 24 saat süreyle reperfüzyona bırakıldı. Melatonin ve amlodipin 10mg/kg ip veya 50µg/sıçan icv dozlarında reperfüzyondan hemen önce uygulandı. Nörolojik tayin sonrası hayvanlar dekapite edildi. Beyin dokularında malondialdehit (MDA) ve glutatyon (GSH) düzeyleri ile myeloperoxidaz (MPO) ve Na+-K+-ATPaz aktiviteleri tayin edildi. Dokuda serbest radikal oluşumu luminol ve lusigenin kemiluminesans (KL) yöntemi ile ölçüldü. Beyin ödemi yaş/kuru ağırlık üzerinden, kan beyin bariyer (KBB) geçirgenliği de Evans Mavisi (EM) extravazasyonu ile değerlendirilidi. Bulgular: Çözücü uygulanan grup ile karşılaştırıldığında nörolojik bozuklukların melatonin ve amlodipin gruplarında düzeldiği belirlendi. İskemi/reperfüzyon beyinde GSH ve Na+-K+-ATPaz aktivitesinde azalma ve bununla birlikte MDA, MPO ve KL düzeylerinde artışa neden oldu. Buna karşılık melatonin ve amlodipin tedavileri tüm incelenen biyokimyasal parametrelerdeki değişimi ve İ/R nin neden olduğu beyin ödemini geri çevirdi. Sonuç: Bu bulgulara göre gerek melatonin ve gerekse amlodipin muhtemelen antioksidan özellikleri aracılığı ile global iskemiye bağlı olarak meydana gelen nörokimyasal ve davranışsal değişikleri module edebileceği düşünülmektedir.

Serebral iskemi/reperfüzyona bağlı oksidan beyin hasarına karşı melatonin ve amlodipinin koruyucu etkileri

Objective: In the present study, we investigated the putative protective effect of melatonin and amlodipine against ischemia/reperfusion (I/R)-induced brain damage. Material and Methods: Wistar albino rats were subjected to 15 min of bilateral carotid artery occlusion followed by 24 h of reperfusion. Melatonin and amlodipine were administered in doses of either 10mg/kg ip or 50µg/rat icv just before reperfusion. After neurological examination the rats were decapitated. In the brain tissue samples, malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) and Na+-K+-ATPase activities, and luminol lucigenin chemiluminescence (CL) were determined. Brain edema was evaluated by the wet-dry weight method, and blood brain barrier (BBB) permeability was evaluated by the Evans Blue (EB) extravasation. Results: The neurological deficit was significantly improved in the melatonin and amlodipine groups when compared with the vehicle-treated groups. Ischemia/reperfusion caused a significant decrease in the brain GSH and Na+-K+-ATPase activity, which was accompanied with significant increases in the MDA level, MPO activity, and CL levels of the brain tissues. On the other hand, both melatonin and amlodipine treatment reversed all these biochemical indices as well as brain water content alterations induced by I/R. Conclusion: These findings suggest that both melatonin and amlodipine effectively modulate neuro-behavioural and neurochemical changes in global ischemia, most probably by virtue of their antioxidant properties.

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