sdü tıp fak derg Medical Journal of Süleyman Demirel University 2602-2109 Süleyman Demirel Üniversitesi 10.17343/sdutfd.1222505 Clinical Sciences Klinik Tıp Bilimleri LİPOPOLİSAKKARİT İLE İNDÜKLENMİŞ HİPOKAMPAL TOKSİSİTEDE RAMELTEON'UN ETKİSİ EFFECT OF RAMELTEON ON LIPOPOLYSACCHARIDE INDUCED HIPPOCAMPAL TOXICITY https://orcid.org/0000-0003-3956-7672 Kaynak Mine SÜLEYMAN DEMİREL ÜNİVERSİTESİ https://orcid.org/0000-0002-7933-0453 Savran Mehtap Süleyman Demirel Üniversitesi Tıp Fakültesi Tıbbi Farmakoloji AD https://orcid.org/0000-0002-1545-035X Aşçı Halil SÜLEYMAN DEMİREL ÜNİVERSİTESİ https://orcid.org/0000-0002-6337-8962 Gülle Kanat SÜLEYMAN DEMİREL ÜNİVERSİTESİ https://orcid.org/0000-0003-3739-9580 İlhan İlter SÜLEYMAN DEMİREL ÜNİVERSİTESİ 06 22 2023 30 2 171 178 12 21 2022 05 22 2023 Copyright © 1994, Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi 1994 Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi

AmaçTıptaki gelişmelere rağmen sepsis dünya çapındahala önemli bir sağlık sorunu olmaya devam etmektedirve beyin dokusu sepsisin erken döneminde hasargören yapılardan biridir. Nöroinflamasyon (NI), septikbeyin hasarında ana mekanizma olarak kabul edilir.Ramelteon (RML), seçici olmayan (MT1/MT2) bir melatoninreseptör agonistidir ve 2005 yılında uykusuzlukendikasyonu için FDA tarafından onaylanmıştır.RML, diğer melatonerjik agonist ilaçlar arasında heriki reseptör alt tipi için nispeten daha yüksek afinitegösterir.Gereç ve YöntemRML'nin lipopolisakarit (LPS) ile indüklenen NI üzerindekikoruyucu etkisini araştırmak için yirmi sekizerkek Wistar Albino sıçan kullanıldı. Kontrol, LPS (5mg/kg, intraperitoneal), RML (8 mg/kg, oral) ve LPS+ RML (LPS'den 45 dakika önce) grupları oluşturuldu.Son ilaç uygulamasından 6 saat sonra sıçanlar sakrifiyeedildi. Hemogram analizi için kan, histopatolojikdeğerlendirme için kortikal ve hipokampal dokulartoplandı.BulgularLPS, lökosit ve nötrofil/lenfosit oranını (NLR) artırırken,lenfosit ve trombosit sayısını azalttı. Buna karşınRML ile, NLR’de anlamlı bir azalma ve trombosit sayısındaanlamlı bir artış izlendi. Histokimyasal değerlendirmedeLPS grubuna ait hipokampal ve kortikalalanlarda belirgin inflamatuar hücre infiltrasyonu veapoptoz gözlendi. RML, bu alanlarda inflamatuar yanıtıve apoptotik cisimleri azalttı.SonuçRML, hipokampusta gözlenen LPS'ye bağlı NI'de antiinflamatuarve antiapoptotik mekanizmalar aracılığıylakoruyucu olabilir.

ObjectiveDespite the advances in medicine, sepsis still remainsa major health problem worldwide and brain tissue isone of the structures damaged in the early period ofsepsis. Neuroinflammation (NI) is considered as themain mechanism in septic brain injury. Ramelteon(RML) is a non-selective (MT1 / MT2) melatoninreceptor agonist and was approved by the FDA in 2005with the indication of insomnia. RML shows relativelyhigher affinity for both receptor subtypes among othermelatonergic agonist drugs.Material and MethodTwenty-eight male Wistar Albino rats were usedto investigate the protective effect of RML onlipopolysaccharide (LPS) induced NI. Control, LPS (5mg/kg, intraperitoneally), RML (8 mg/kg, orally) andLPS + RML (45 minutes before LPS) groups werecreated. Six hours following the last drug administration,rats were sacrificed. Blood for hemogram analysis andcortical and hippocampal tissues for histopathologicalevaluation were collected.ResultsLPS increased white blood cell and neutrophil/lymphocyte ratio (NLR) while it decreased lymphocyteand platelet counts. RML decreased NLR andincreased platelet counts significantly. In histochemicalevaluation, marked inflammatory cell infiltration andapoptosis were observed in both hippocampal andcortical areas of LPS group. RML decreased theinflammatory response and apoptotic bodies in theseareas.ConclusionRML may be protective on LPS-induced NI observed inhippocampus via anti-inflammatory and anti-apoptoticmechanisms.

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