L-CITRULLINE ATTENUATES NEUROBEHAVIORAL DEFICITS, AND OXIDATIVE STRESS IN ROTENONE-INDUCED PARKINSON`S DISEASE IN MALE WISTAR RATS

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss in the substantia nigra, leading to motor and non-motor dysfunctions. Oxidative stress and mitochondrial impairment are central mechanisms in its pathogenesis. Although current therapies primarily provide symptomatic relief, they do not significantly halt disease progression. This study investigated the potential neuroprotective effect of L-citrulline in a rotenone-induced Parkinson’s disease model in male Wistar rats. Forty adult male Wistar rats were divided into four groups: control, rotenone, rotenone + L-citrulline (100 mg/kg), and rotenone + L-citrulline (200 mg/kg). Parkinsonism was induced using rotenone (2.5 mg/kg, intraperitoneally) for 14 days, followed by 21 days of oral L-citrulline treatment. Behavioral assessment was conducted using the open field test to assess locomotor and anxiety-like behaviours. Biochemical analyses of brain tissues measured malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels to assess oxidative stress status. Rotenone administration significantly impaired locomotor and exploratory behaviors while increasing anxiety-like activities. It also reduced SOD and catalase activities and elevated MDA levels, indicating severe oxidative stress. L-citrulline treatment dose-dependently improved behavioral performance, restored locomotor activity, and reduced freezing behavior. Biochemically, it significantly enhanced antioxidant enzyme activity while reducing lipid peroxidation, with the 100 mg/kg dose showing more pronounced MDA reduction than 200 mg/kg. L-citrulline demonstrates significant neuroprotective potential in a rotenone-induced PD model through restoration of antioxidant defenses, reduction of oxidative damage, and improvement of motor and behavioral outcomes. These findings suggest its possible role as a disease-modifying adjunct in Parkinson’s disease.