Title:Agmatine Improves Oxidative Stress Profiles in Rat Brain Tissues Induced by Sodium Azide
Volume: 18
Issue: 3
Author(s): Hira Rafi*, Hamna Rafiq and Muhammad Farhan
Affiliation:
- Neurochemistry and Biochemical Neuropharmacology Research Unit, Department of Biochemistry, University of
Karachi, Karachi, Pakistan
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Keywords:
Agmatine, sodium azide, oxidative stress, antioxidative enzymes, reactive oxygen species, behaviors, neurodegeneration.
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.
