Effects of Amitriptyline on the Experimental Acute and Chronic Inflammation Models

Year 2018, Volume: 2 Issue: 2, 160 - 172, 31.08.2018

Candan Dalkılıç Günnur Özbakış Dengiz , Murat İnanç Cengız , Zehra Kurçer , Zekiye Nur Banoğlu

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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