Citrate-coated silver nanoparticles loaded with agomelatine provide neuronal therapy in acute cerebral ischemia/reperfusion of rats by inhibiting the oxidative stress, endoplasmic reticulum stress, and P2X7 receptor-mediated inflammasome.

Abstract

Cerebral ischemia and reperfusion are related to various situations like injuries after various traumas, oxidative stress, increased calcium ion, capillary hypoperfusion, microvascular hyperpermeability, leukocyte infiltration, and blood-brain barrier disruption. An antidepressant Agomelatine which is a melatonin receptor (MT1/MT2) agonist and serotonin receptor (5-HT2C) antagonist has been reported by studies to have antioxidant and anti-inflammatory effects. In our study, we aimed to detect the effects of citrate-coated silver nanoparticle-loaded agomelatine application on neurodegeneration, endoplasmic reticulum stress, autophagic and apoptotic cell death, inflammation, and P2X7R expression in the cerebral ischemia-reperfusion model to facilitate the passage of blood-brain barrier. Forty two Sprague-Dawley rats in total were divided into six equal groups (n:7) and applications were performed. Acute cerebral injury in the ischemia-reperfusion model was created 2 h after internal carotid artery ligation in rats and then at the 2nd hour of reperfusion citrate-coated silver nanoparticles loaded with Agomelatine were applied. Twenty four hours later, neurologic analysis on animals in experimental groups was performed, animals were decapitated and GSH, GPx, SOD, CAT, MDA, IL-1β, and TNF-α parameters were examined after taking blood and the cerebral tissue samples. As a result, it was determined that ischemia-reperfusion caused endoplasmic reticulum stress in the cerebral tissues and thus caused cellular injury.