EFFECT OF RAMELTEON ON LIPOPOLYSACCHARIDE INDUCED HIPPOCAMPAL TOXICITY.

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. [ABSTRACT FROM AUTHOR]