Effects of Amitriptyline on the Experimental Acute and Chronic Inflammation Models

Abstract

Amitriptyline is a tricyclic antidepressant and antagonizes serotonergic, adrenergic, histaminergic and some cholinergic receptors and blocks sodium, calcium and potassium channels which has affects on inflammmation pathophysiology. The aim of our study is to examine the anti-inflammatory effect (AIE) of amitriptyline on acute and chronic inflammation models in rats. In our study acute inflammation was created with carrageenan and histamine induced paw edema models in rats. After measuring the basal right hind paw volumes of rats, distilled water for the control group, diclofenac sodium and amitriptyline (5- 10 and 20 mg/kg for carrageenan model, 10 mg/kg for histamine model) for the other groups were injected intraperitoneally. After 30 minutes, paw edema was induced by injection of 1% carrageenan solution or 0.1% histamine solution into sub-plantar region of the same right hind paws. Following the injections paw volumes were measured 5 times at 1 hour intervals (for carrageenan injection) and 6 times at 30 minutes intervals (for histamine injection). The AIE’s of amitriptyline injected groups were calculated based on the increase of paw edema volumes of the control group. AIE effect of amitriptyline on the chronic phase of inflammation were tested with Cotton-Pellet granuloma method. The obtained results were analyzed by ANOVA and post-hoc LSD test. Amitriptyline, 10 mg/kg, showed significant AIE at 1 and 2 hours (52.56% and 46.43%) in carrageenan-induced paw edema model (p<0.05) and at 30, 60, 90, 120 and 150 minutes (in order of 46.23%, 40.05%, 43.34%, 47.67% and 52.94%) in histamine-induced paw edema model (p<0.05). In Cotton-Pellet granuloma model, amitriptyline showed significantly anti-proliferative effect based on the wet and dry cotton pellets weights removed from rats (in order of 26.62%, 31.09%) (p< 0.05). Amitriptyline showed both acute ve chronic AIE. The acute AIE of amitriptyline may be due to the inhibition of some neuromediators (especially histamine) on the early phase of inflammation. Chronic AIE may be useful for the treatment of some chronic inflammatory diseases accompanied with depression.

Amitriptilinin Deneysel Akut ve Kronik İnflamasyon Modelleri Üzerine Etkisi

Abstract

Amitriptilin, inflamasyon fizyopatolojisinde etkili olan serotonerjik, adrenerjik, histaminerjik ve bazı kolinerjik reseptörleri antagonize, sodyum, kalsiyum ve potasyum kanallarını bloke ettiği bildirilen trisiklik bir antidepresandır. Çalışmamızın amacı amitriptilinin sıçanlarda oluşturulan akut ve kronik inflamasyon modellerinde antiinflamatuvar etkilerini (AİE) araştırmaktır. Çalışmamızda akut inflamasyon sıçan pençe modelinde karragenin ve histamin ile oluşturuldu. Sıçanların sağ arka ayak hacimleri ölçülerek, kontrol grubuna distile su, diğer gruplara diklofenak sodyum ve amitriptilin (karragenin modelinde 5- 10 ve 20 mg/kg- histamin modelinde 10 mg/kg) intraperitoneal uygulandı ve 30 dakika sonra, aynı ayaklarda %1’lik karagenin veya %0.1 ’lik histamin ile inflamasyon oluşturuldu. Karragenin inflamasyonunu takiben, 1 saat ara ile 5 kez, histamin inflamasyonunu takiben, 30 dakika ara ile 6 kez hayvanların pençeleri ölçüldü. Amitriptilin gruplarının AİE’leri kontrol grubu pençe ödemi artışlarına göre hesaplandı. Çalışmamızda, amitriptilinin kronik AİE’si koton-pellet granüloma testi ile değerlendirildi. Elde edilen sonuçlar ANOVA ve post-hoc LSD testi ile analiz edildi. Amitriptilin, karragenin modelinde, sadece 10 mg/kg dozda 1. ve 2. saatlerde %52.56 ve 46.43’lük AİE göstermiştir (p<0.05). Histamin modelinde ise, amitriptilin 30, 60, 90, 120 ve 150. dakikalarda sırasıyla %46.23, 40.05, 43.34, 47.67 ve 52.94 oranlarında AİE sergilemiştir (p<0.050). Koton-pellet granüloma testinde, amitriptilin uygulanan grupta pamuk bilyelerin yaş ağırlıklarında %26.62’lik, kuru ağırlıklarında ise %31.09’luk anti-proliferatif etki tespit edilmiştir (p<0.05). Sonuç olarak, amitriptilin akut ve kronik AİE göstermiştir. Akut AİE’si, inflamasyonun erken fazında salınan bazı nöromediyatörlerin (özellikle histamin) inhibisyonuna bağlı olabilir. Kronik AİE’ye sahip olması ise depresyonla seyreden bazı kronik inflamatuvar hastalıkların tedavilerinde yer alabilir.

Keywords

• Amitriptilin,inflamasyon,histamin,karragenin,koton-pellet,sıçan

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