LİPOPOLİSAKKARİT İLE İNDÜKLENMİŞ HİPOKAMPAL TOKSİSİTEDE RAMELTEON'UN ETKİSİ

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.