Agmatine Improves Oxidative Stress Profiles in Rat Brain Tissues Induced by Sodium Azide

Abstract

Introduction: The brain is highly susceptible to oxidative damage due to excessive oxygen tension, a high concentration of oxidizable substrates, and low antioxidant capacity. Consequently, oxidative stress is linked to several brain disorders and neurodegeneration. Sodium azide is a cytochrome oxidase inhibitor that promotes neurodegeneration by enhancing the release of excitotoxins and inducing oxidative stress through the peroxidation of membrane lipids. This process results in the release of intra-mitochondrial Ca+2 and H2O2 (ROS Dependent-Ca+2 release). Agmatine, a biogenic amine, is also referred to as a free radical scavenger, protecting the brain from membrane collapse, apoptosis, and mitochondrial swelling. Objective: This study was designed to identify the antioxidative effects of agmatine on sodium azide- induced oxidative stress in brain tissues. Methodology: Twenty-four male albino Wistar rats were allocated into two groups: a control group receiving water and a test group administered sodium azide (5 mg/kg, intraperitoneally) for a duration of 14 days. Subsequently, the animals were further subdivided and treated for an additional two weeks with either water or agmatine (100 mg/kg). Behavioral assessments were performed onehour post-agmatine administration, and brain homogenates were prepared for biochemical analyses. Results: The agmatine-treated group exhibited a significant increase (P<0.01) in both the number of entries and the time spent in the light box and the open arms of the light/dark transition box and elevated plus maze tests, respectively. Additionally, agmatine administration significantly enhanced (P<0.01) the total number of squares crossed in the open field test. Biochemical assessments revealed that agmatine treatment significantly reduced (P<0.01) the levels of reactive oxygen species and malondialdehyde. Moreover, it significantly increased (P<0.01) the levels of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and glutathione compared to the control group. Conclusion: The present study revealed that agmatine has substantial effects on oxidative and antioxidant enzyme levels in sodium azide-induced oxidative stress. Agmatine-treated rats exhibited decreased reactive oxygen species levels and improvements in behavioral impairments resulting from sodium azide administration.