The Neuroprotective Effects of Curcumin Nanoparticles on The Cerebral Ischemia-Reperfusion Injury in The Rats-The Roles of The Protein Kinase RNA-Like ER Kinase/Extracellular Signal-Regulated Kinase and Transcription Factor EB proteins.

Abstract

Reduction of cerebral ischemia-reperfusion injury (IRI)/re-oxygenation injury, is defined as the paradoxical exacerbation of the cellular dysfunction and death, following restoration of the blood flow to previously ischemic tissues. The re-establishment of blood flow is essential to salvage the ischemic tissues. As a result, the treatment of IRI with novel therapies, which have fewer side effects, are of great importance. Therefore, this study aimed to investigate the effects of curcumin nanoparticle (CN) pre-treatment on the cerebral I/R rat model. In this experimental study, CN was administered to rats orally five days before the bilateral common carotid artery occlusion (BCCAO) and continued for three days. The intensity of oxidative stress, the activities of antioxidant enzymes, glutathione (GSH) content, the activity of mitochondrial enzymes, including succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and lactate dehydrogenase (LDH), curcumin bioavailability, pERK/ERK expression ratio and TFEB protein were studied. Data analysis was performed using Graphpad Prism V.8 software, one-way analysis of variance (ANOVA) with the statistical package for the social sciences (SPSS V.26 software). Cerebral IRI-damage significantly increased the oxidative stress (P=0.0008) and decreased the activity of the antioxidant enzymes including catalase (CAT) (P<0.001), super oxide dismutase (SOD) (P<0.001), reduced GSH (P<0.001), mitochondrial enzymes, pERK/ERK expression ratio (P=0.002) and TEFB protein (P=0.005) in rats' brains. In addition, the pre-treatment of the rats with CN resulted in a decrease in the reactive oxygen species (ROS), and an increase in the activities of antioxidants and mitochondrial enzymes. This in turn up-regulated the pERK/ERK expression ratio and TEFB expression. CN has neuroprotective effects on the cerebral IRI condition due to its antioxidant properties and is able to overexpress the pERK and TFEB proteins; thus, it can be considered as a suitable treatment option during and after the incidence of stroke.