Cerium oxide nanoparticles could ameliorate behavioral and neurochemical impairments in 6-hydroxydopamine induced Parkinson's disease in rats

• Published in: Neurochemistry international 2017-09, Vol.108, p.361-371
• Main Authors: Hegazy, Maha A., Maklad, Hala M., Samy, Doaa M., Abdelmonsif, Doaa A., El Sabaa, Bassma M., Elnozahy, Fatma Y.
• Format: Article
• Language: English
• Subjects: 6-hydroxydopamine; Animals; Apoptosis; Cerium - pharmacology; Cerium - therapeutic use; Cerium oxide nanoparticles; Corpus Striatum - drug effects; Corpus Striatum - pathology; Corpus Striatum - ultrastructure; Dose-Response Relationship, Drug; Locomotion - drug effects; Locomotion - physiology; Male; Nanoparticles - therapeutic use; Oxidative stress; Oxidopamine - toxicity; Parkinson's disease; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - drug therapy; Parkinsonian Disorders - pathology; Rats; Rats, Wistar; Striatal dopamine
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2017.05.011

Cerium oxide nanoparticles (CeO2NPs) showed promising effects in neurodegenerative diseases including some animal models of Parkinsonism. However, the implication of CeO2NPs in 6-hydroxydopamine (6-OHDA) induced Parkinsonism remains to be investigated. This study was designed to assess whether CeO2NPs treatment could alleviate neurobehavioral and neurobiochemical deficits in 6-OHDA induced neurotoxicity in rats. 50 rats received left intrastriatal (IS) injection of either saline (control, n = 10) or 6-OHDA (n = 40). At the third week post-lesion, motor dysfunction was verified using neurobehavioral tests. Then diseased rats received intraperitoneal injection of 0.1, 0.5 or 1 mg/kg of CeO2NPs or vehicle (10 rats each) for 3 weeks. Rats were subjected to behavioral assessments and then sacrificed for biochemical analyses of the striatum. Striatal dopamine levels, oxidative stress markers including total antioxidant capacity (TAC) and malondialdehyde (MDA), and caspase 3 activity as an apoptotic marker were assessed. Different doses of CeO2NPs variably improved motor dysfunctions induced by 6-OHDA injection in open field, Rota Rod and stepping tests. In addition, the neurobiochemical derangements were almost reversed by the 0.5 mg/kg dose of CeO2NPs, while 0.1 mg/kg dose was not sufficient to alter biochemical measurements in the striatum. Administration of 1 mg/kg of CeO2NPs partially ameliorated striatal dopamine and decreased apoptosis without significant effect on oxidative stress. The present study showed a putative therapeutic role of CeO2NPs in the treatment of 6-OHDA-induced Parkinsonian rats, and suggested their antioxidant and antiapoptotic effects as possible mechanisms for elevated striatal dopamine level and improved motor performance. •CeO2NPs treatment improved motor deficits in 6-OHDA induced-Parkinsonism in rats.•CeO2NPs increased striatal dopamine and ameliorated oxidative stress and apoptosis.•CeO2NPs at 0.5 mg/kg dose showed superior therapeutic effects than 0.1 and 1 mg/kg.•The 1 mg/kg CeO2NPs dose seemed neurotoxic to striatal tissues.