EFFECT OF RAMELTEON ON LIPOPOLYSACCHARIDE INDUCED HIPPOCAMPAL TOXICITY

Year 2023, , 171 - 178, 22.06.2023

Mine Kaynak , Mehtap Savran , Halil Aşçı , Kanat Gülle , İlter İlhan

https://doi.org/10.17343/sdutfd.1222505

Abstract

Objective
Despite the advances in medicine, sepsis still remains
a major health problem worldwide and brain tissue is
one of the structures damaged in the early period of
sepsis. Neuroinflammation (NI) is considered as the
main mechanism in septic brain injury. Ramelteon
(RML) is a non-selective (MT1 / MT2) melatonin
receptor agonist and was approved by the FDA in 2005
with the indication of insomnia. RML shows relatively
higher affinity for both receptor subtypes among other
melatonergic agonist drugs.
Material and Method
Twenty-eight male Wistar Albino rats were used
to investigate the protective effect of RML on
lipopolysaccharide (LPS) induced NI. Control, LPS (5
mg/kg, intraperitoneally), RML (8 mg/kg, orally) and
LPS + RML (45 minutes before LPS) groups were
created. Six hours following the last drug administration,
rats were sacrificed. Blood for hemogram analysis and
cortical and hippocampal tissues for histopathological
evaluation were collected.
Results
LPS increased white blood cell and neutrophil/
lymphocyte ratio (NLR) while it decreased lymphocyte
and platelet counts. RML decreased NLR and
increased platelet counts significantly. In histochemical
evaluation, marked inflammatory cell infiltration and
apoptosis were observed in both hippocampal and
cortical areas of LPS group. RML decreased the
inflammatory response and apoptotic bodies in these
areas.
Conclusion
RML may be protective on LPS-induced NI observed in
hippocampus via anti-inflammatory and anti-apoptotic
mechanisms.

Keywords

Lipopolysaccharide, Hippocampus, Ramelteon, Neuroinflammation

Supporting Institution

“The Scientific Research Projects Coordination Unit of Süleyman Demirel University"

Project Number

TYL-2020-8048

LİPOPOLİSAKKARİT İLE İNDÜKLENMİŞ HİPOKAMPAL TOKSİSİTEDE RAMELTEON'UN ETKİSİ

Abstract

Amaç
Tıptaki gelişmelere rağmen sepsis dünya çapında
hala önemli bir sağlık sorunu olmaya devam etmektedir
ve beyin dokusu sepsisin erken döneminde hasar
gören yapılardan biridir. Nöroinflamasyon (NI), septik
beyin hasarında ana mekanizma olarak kabul edilir.
Ramelteon (RML), seçici olmayan (MT1/MT2) bir melatonin
reseptör agonistidir ve 2005 yılında uykusuzluk
endikasyonu için FDA tarafından onaylanmıştır.
RML, diğer melatonerjik agonist ilaçlar arasında her
iki reseptör alt tipi için nispeten daha yüksek afinite
gösterir.
Gereç ve Yöntem
RML'nin lipopolisakarit (LPS) ile indüklenen NI üzerindeki
koruyucu etkisini araştırmak için yirmi sekiz
erkek Wistar Albino sıçan kullanıldı. Kontrol, LPS (5
mg/kg, intraperitoneal), RML (8 mg/kg, oral) ve LPS
+ RML (LPS'den 45 dakika önce) grupları oluşturuldu.
Son ilaç uygulamasından 6 saat sonra sıçanlar sakrifiye
edildi. Hemogram analizi için kan, histopatolojik
değerlendirme için kortikal ve hipokampal dokular
toplandı.
Bulgular
LPS, lökosit ve nötrofil/lenfosit oranını (NLR) artırırken,
lenfosit ve trombosit sayısını azalttı. Buna karşın
RML ile, NLR’de anlamlı bir azalma ve trombosit sayısında
anlamlı bir artış izlendi. Histokimyasal değerlendirmede
LPS grubuna ait hipokampal ve kortikal
alanlarda belirgin inflamatuar hücre infiltrasyonu ve
apoptoz gözlendi. RML, bu alanlarda inflamatuar yanıtı
ve apoptotik cisimleri azalttı.
Sonuç
RML, hipokampusta gözlenen LPS'ye bağlı NI'de antiinflamatuar
ve antiapoptotik mekanizmalar aracılığıyla
koruyucu olabilir.

Keywords

Lipopolisakkarit, Hipokampus, Ramelteon, Nöroinflamasyon

Project Number

TYL-2020-8048

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