Exenatideas Neuroprotectivevia Reducing Inflammation and Oxidative stress in Ischemic/Reperfusion of Adult Animal Rats

Abstract

Background: Stroke is considered a major cause of death and disability worldwide. The most important mechanisms that lead to stroke are thrombotic occlusion, embolic occlusion, and vascular rupture (hemorrhage). Unfortunately, there has been only one pharmacological agent approved to treats stroke, recombine antalteplase agent(rtPA), and should be used within 4-5 h from onset of stroke with accurate diagnosis. Due to these difficulties, more than 10% of stroke patients were not received rtPA.Exenatide is incretin mimetic agent which mimics the action of the endogenous glucagon like peptide-1(GLP-1). Exenatide is approved as adjunctive therapy for patient with type2 diabetes [1-2].it is injected subcutaneously and the peak concentration reaches approximately within 2 hours with the duration of action 10 hours. Apart from its antidiabetic action, it’s playing an important role in the GLP-1 receptors distributed on neuronal tissues. GLP-1 and its receptors had a beneficial role as neuronal protective, anti-inflammatory,and anti-oxidant agent as well as in neuronal learning & memory,so, the present study aimed the explore the neuroprotective effect of Exenatide.

Method: Adult twenty-four Sprague-Dawley rats has been divided randomly into four equal groups. Sham group just undergone anesthesia at same time and condition of other groups. Control which undergone induction of ischemia 30 mints then reperfusion 60 mints. Vehicle group the same control group but differs by injected intraperitoneally the vehicle (1ml/kg of 10% of DMSO) of treatment before 120 mints from reperfusion. Treatment groups the same control group but differs from them by treated intraperitoneallywith (2µg/kg) of Exenatide before 120 mints.

Results:the induction of ischemia/reperfusion in rats (control group)significantly (P≤0.05) increased the levels of IL-1β, MMP-9, 8-iso-PGF2α, as well asICAM-1. Exenatide at dose (2µg/kg) significantly (P≤0.05) loweringthe levels ofIL-1β, MMP-9, 18-iso-PGF2α, as well asICAM-.

Conclusions:decrease in pro inflammatory agent IL-1β, MMP-9, ICAM-1, and oxidative stress 8-iso-PGF2α in grouptreated with Exenatide drug consider as neuroprotective for cerebral ischemia/reperfusion in male rat model.