Protective Activity of Citicoline Against Neurobehavioral and Cerebellar Histo-biochemical Derangement Induced by Nickel Chloride: Role of Caspase-3 and NRF2

Idemudia OU; Ewelinwa C; Aig-Unuigbe JE; Tobalu FO; Orheruata AR; Enogieru AB

doi:10.61386/imj.v19i4.1376

Authors

Idemudia OU Department of Anatomy, University of Benin, Benin City, Nigeria
Ewelinwa C Department of Anatomy, University of Benin, Benin City, Nigeria
Aig-Unuigbe JE Department of Anatomy, University of Benin, Benin City, Nigeria
Tobalu FO Department of Anatomy, University of Benin, Benin City, Nigeria
Orheruata AR Department of Anatomy, University of Benin, Benin City, Nigeria
Enogieru AB Department of Anatomy, University of Benin, Benin City, Nigeria

DOI:

https://doi.org/10.61386/imj.v19i4.1376

Keywords:

Citicoline, Nickel chloride, Cerebellum, Caspase-3, NRF2

Abstract

Context: Nickel chloride (NiCl2) is a widely used industrial compound that poses significant neurotoxic risks through mechanisms involving oxidative stress, apoptosis, and neuronal degeneration. The cerebellum is particularly susceptible to such insults due to its role in motor coordination and locomotor control.

Objective: The study investigated the neuroprotective potential of citicoline against NiCl2-induced cerebellar toxicity in adult Wistar rats.

Materials and Methods: Forty-two adult Wistar rats were randomly assigned to six groups and treated for 28 days as follows: I (Control), II (5mg/kg NiCl2), III (250 mg/kg citicoline + 5mg/kg NiCl2), IV (500 mg/kg citicoline + 5mg/kg NiCl2), V (250 mg/kg citicoline) and VI (250 mg/kg citicoline). Neurobehavioural assessments were performed using the Open Field Test, String Test, and Movement Initiation Test. Oxidative stress markers, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH), were evaluated in cerebellar homogenates. Histological examination of the cerebellum was conducted, while molecular docking studies were performed to investigate the interaction of citicoline with Caspase-3 and nuclear factor erythroid 2-related factor 2 (NRF2).

Results: Compared to control, NiCl2 significantly (p < 0.05) impaired locomotor and motor performance and induced oxidative stress (decreased SOD, CAT, GPx, and GSH; increased MDA), alongside histological evidence of Purkinje cell degeneration, nuclear pyknosis, and cerebellar layer vacuolations. Citicoline significantly (p < 0.05) reversed these behavioural, biochemical, and histological alterations when compared to rats treated with NiCl2 only, and showed favourable docking affinities towards Caspase-3 and NRF2.

Conclusion: Citicoline protects against NiCl₂-induced cerebellar toxicity by attenuating oxidative stress and possibly modulating apoptotic pathways, thus preserving neuronal integrity and highlighting its therapeutic potential for heavy metal-induced neurodegeneration and motor dysfunction.