EFFECT OF RAMELTEON ON LIPOPOLYSACCHARIDE INDUCED HIPPOCAMPAL TOXICITY

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

Makale detayları

EFFECT OF RAMELTEON ON LIPOPOLYSACCHARIDE INDUCED HIPPOCAMPAL TOXICITY

Yazarlar:

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

Yayıncı:

Süleyman Demirel University

Ana Başlıklar:

Clinical Sciences

Dergi:

Medical Journal of Süleyman Demirel University Vol.30 Issue 2, pp.171-178

Belge Tipi:

Makale

Yayın Tarihi:

6/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001292478

pISSN:

1300-7416

Anahtar kelimeler:

Özet:

 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 mgkg, intraperitoneally, RML 8 mgkg, 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.

 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 mgkg, intraperitoneally, RML 8 mgkg, 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.

 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 mgkg, intraperitoneally, RML 8 mgkg, 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.

 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 MT1MT2 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 RMLnin lipopolisakarit LPS ile indüklenen NI üzerindeki koruyucu etkisini araştırmak için yirmi sekiz erkek Wistar Albino sıçan kullanıldı. Kontrol, LPS 5 mgkg, intraperitoneal, RML 8 mgkg, oral ve LPS  RML LPSden 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 nötrofillenfosit oranını NLR artırırken, lenfosit ve trombosit sayısını azalttı. Buna karşın RML ile, NLRde 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 LPSye bağlı NIde antiinflamatuar ve antiapoptotik mekanizmalar aracılığıyla koruyucu olabilir.

Makale detayları

EFFECT OF RAMELTEON ON LIPOPOLYSACCHARIDE INDUCED HIPPOCAMPAL TOXICITY

Yazarlar:

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

Yayıncı:

Süleyman Demirel University

Ana Başlıklar:

Clinical Sciences

Dergi:

Medical Journal of Süleyman Demirel University Vol.30 Issue 2, pp.171-178

Belge Tipi:

Makale

Yayın Tarihi:

6/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001292478

pISSN:

1300-7416

Lipopolysaccharide

Hippocampus

Ramelteon

NeuroinflammationLipopolisakkarit

Hipokampus

Ramelteon

Nöroinflamasyon

Sayı

Makale detayları

Yazarlar: Mine Kaynak | Mehtap Savran | Halil Aşçı | Kanat Gülle | İlter İlhan

Yayıncı: Süleyman Demirel University

Ana Başlıklar: Clinical Sciences

Dergi: Medical Journal of Süleyman Demirel University Vol.30 Issue 2, pp.171-178

Belge Tipi: Makale

Yayın Tarihi: 6/2023

Belge Dili: İngilizce

Document ID (Org No.): 2001292478

pISSN: 1300-7416

Sayı

Yazarlar:

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

Yayıncı:

Süleyman Demirel University

Ana Başlıklar:

Clinical Sciences

Dergi:

Medical Journal of Süleyman Demirel University Vol.30 Issue 2, pp.171-178

Belge Tipi:

Makale

Yayın Tarihi:

6/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001292478

pISSN:

1300-7416