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

Abstract

Background: 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.

Aim: This study was designed to assess whether CeO₂NPs treatment could alleviate neurobehavioral and neurobiochemical deficits in 6-OHDA induced neurotoxicity in rats.

Material and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: 6-Hydroxydopamine (PubChem CID: 176170); 6-hydroxydopamine; Apoptosis; Cerium oxide (PubChem CID: 73963); Cerium oxide nanoparticles; Oxidative stress; Parkinson's disease; Striatal dopamine.