Inhibition of Oxidative Stress and the NF-ΚB Pathway by a Vitamin E Derivative: Pharmacological Approach against Parkinson's Disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder. In this study, PD was induced via (ip) injection of haloperidol (1 mg/kg/day). Animals were divided into seven groups (n = 70). Group I received the vehicle carboxymethylcellulose (CMC; 0.5%), group II was treated with designated 1 mg/kg haloperidol, and group III received the standard drug Sinemet (100 mg/kg), while groups IV-VII received a tocopherol derivative (Toco-D) at dose levels of 5, 10, 20, and 40 mg/kg, respectively, via the oral route. All groups received haloperidol for 23 consecutive days after their treatments except the control group. The improvement in locomotor activity and motor coordination was evaluated by using behavioral tests. Oxidative stress markers, neurotransmitters, and monoamine oxidase B (MAO-B) as well as NF-kappa B levels in the whole brain were measured. mRNA expression analysis of alpha-synuclein was carried out using the PCR technique. Toco-D at 20 mg/kg showed the maximum improvement in locomotor activity. The levels of antioxidant enzymes and neurotransmitters were also increased by the treatment with Toco-D. Inflammatory cytokine levels and mRNA expression of alpha-synuclein were decreased by Toco-D in treated animals. This study concluded that Toco-D might be effective in the improvement of locomotor activity and motor coordination in haloperidol-induced PD.

Automated summary

This study found that Toco-D may be effective in improving locomotor activity and motor coordination in haloperidol-induced Parkinson's disease. Toco-D increased antioxidant enzyme and neurotransmitter levels, while decreasing inflammatory cytokine levels and mRNA expression of alpha-synuclein.