Modafinil Alleviates Rotenone-Induced Neurochemical changes and Striatal Neurodegeneration via Inhibiting Oxidative Stress and Neuroinflammation | ||||
Egyptian Journal of Chemistry | ||||
Article 32, Volume 63, Issue 12, December 2020, Page 5027-5037 PDF (1.07 MB) | ||||
Document Type: Original Article | ||||
DOI: 10.21608/ejchem.2020.47734.2975 | ||||
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Authors | ||||
Sara Ahmed Seadawy 1; Marwa El-Sayed El-Shamarka 2; Mie Afify 3; Omar Abdel-Salam 4; Dalia abouefadle5 | ||||
1Biochemistry department, Genetic engineering and biochemistry research division, National Research Centre. El-Behowth St., Dokki, Cairo, Egypt. | ||||
2Medical Research Division Research division,Narcotics, Ergogenics and Poisons Department,Cairo,Egypt | ||||
3Biochemistry Dept. NRC | ||||
4Department of Toxicology and Narcotics, National Research Centre, Dokki, Cairo, egypt | ||||
5Department of Pathology, Medical Division, National Research Centre, Cairo, Egypt | ||||
Abstract | ||||
Objectives of study are around investigation the effect of the central nervous system stimulant modafinil on brain striatum neurodegeneration caused by subcutaneous (s.c.) rotenone administration in rats, further, the possible modulation by modafinil on L-dopa effect on oxidative stress, inflammation and nigrostriatal cell damage. Seven groups of Male albino mice received dimethyl sulfoxides.c., rotenone (1.5 mg/kg, s.c., 3 times per week), rotenone/L-dopa (25 mg/kg, p.o., daily), rotenone/modafinil (0.1, 0.2 and 0.3 mg/kg respectively, p.o., daily), rotenone/L-dopa/modafinil (0.2 mg/kg, p.o. daily). The treatment was continued for 2 weeks. Mice were tested for behavioral changes 24h after the end of treatments.Mice were evaluated for brain biochemical markers of oxidative stress (lipid peroxidation, reduced glutathione, and nitric oxide), pro-inflammatory factors (tumor necrosis factor-α, interlukin-1beta) and dopamine level. Histopathologic examination and the expression of the anti-apoptotic protein caspase-3 were also performed. Rotenone significantly elevated oxidative stress and pro-inflammation, decreased dopamine, induced substantianigra damage with caspase-3-mediated apoptosis respectly to the control levels. Results of modafinil or its combination with L-dopa may have potential therapeutic effect in Parkinson’s disease by decreasing pro-inflammation and oxidative stress, increasing dopamine, preventing the development of neuronal damage and reducing caspase-3 expression in the striatum. | ||||
Keywords | ||||
Modafinil; Brain oxidative stress; neuro-inflammation; apoptosis; nigrostriatal damage; rotenone; L-dopa | ||||
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