Deferoxamine halt rotenone-induced Parkinson's like symptoms in experimental rats: biochemical, neuroinflammatory, neurotransmitters, and histological evidence.

Abstract

Rotenone is a pesticide compound that selectively damages dopaminergic neurons in the substantia nigra pars compacta and produces Parkinson's like symptoms in rodents. Deposition of iron and reactive oxygen species (ROS) generation by its oxidation are contributing factors in the etiology of Parkinson's disease. Deferoxamine (DFO) is an iron chelator with high affinity produced by Streptomyces wadayamensis, S. malaysiense, like organisms. The present study provides insight to evaluate the protective effect of DFO in rotenone-induced neurotoxicity in rats. Rotenone (6 μg/2 μl/rat, unilaterally) was injected intranigral on day-1 using a digital stereotaxic apparatus. DFO (50 and 100 mg/kg, intraperitoneally) was given orally daily for 21 days starting from day 8 after the intranigral surgery. On day 28, animals were sacrificed, and the striatum was isolated for oxidative stress parameters (lipid peroxidation, nitrite and reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase), neuroinflammatory cytokines (IL-1β, IL-6, and TNF-α), mitochondrial complexes-I and IV, neurotransmitters (brain catecholamines, gamma-aminobutyric acid, glutamate), and iron level estimation. Unilateral intranigral infusion of rotenone led to significant motor deficits as evidenced by impairments in locomotor activity in open field test, rotarod activity (motor coordination), grip strength, and narrow beam walk performance. DFO administration dose-dependently significantly improved against rotenone-induced behavioral abnormalities in rats, restored the altered level of neurotransmitters in the striatum, and attenuated oxidative stress and inflammatory response in the striatum. These findings indicate that DFO successfully achieved antioxidant and anti-inflammatory properties and protect dopaminergic neurons against rotenone-induced neurotoxicity.