Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
Pharmacol Rep. 2013;65(5):1213-26. doi: 10.1016/s1734-1140(13)71479-8.
Parkinson's disease is a neurodegenerative disorder of uncertain pathogenesis characterized by a loss of dopaminergic neurons in substantia nigra pars compacta, and can be modeled by the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The current research was directed to investigate the role of melatonin in preventing the gradual decrease in the response to L-dopa in MPTP-induced parkinsonism in mice.
Eighty four male Swiss mice were divided into seven groups. Group I is the saline group. The other six groups were injected with MPTP (20 mg/kg/2 h). Group II is the MPTP control group. Group III was treated with L-dopa/carbidopa (100/10 mg/kg, po). Group IV and V were treated with melatonin (5 or 10 mg/kg, po), respectively. Group VI and VII received L-dopa/carbidopa in combination with melatonin in the same above-mentioned doses, respectively.
Results showed that MPTP-treated mice exhibited low striatal dopamine level accompanied by motor impairment and increased oxidative stress. Treatment with L-dopa improved the motor performance of mice. Addition of melatonin to L-dopa therapy improved the motor response to L-dopa and increased striatal dopamine level. This combination reduced lipid peroxidation, ameliorated reduced glutathione and improved antioxidant enzyme activities (p ≤ 0.05).
Overall, our study suggests that the antioxidant potential of melatonin makes it a promising candidate to L-dopa in treating Parkinson's disease.
帕金森病是一种病因不明的神经退行性疾病，其特征是黑质致密部多巴胺能神经元丧失，可通过神经毒素 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）建模。本研究旨在探讨褪黑素在预防 MPTP 诱导的帕金森病小鼠对 L-多巴反应逐渐下降中的作用。
84 只雄性瑞士小鼠分为 7 组。第 I 组为生理盐水组。其余 6 组给予 MPTP（20mg/kg/2h）注射。第 II 组为 MPTP 对照组。第 III 组给予 L-多巴/卡比多巴（100/10mg/kg，po）治疗。第 IV 组和第 V 组分别给予褪黑素（5 或 10mg/kg，po）治疗。第 VI 组和第 VII 组分别给予 L-多巴/卡比多巴联合上述剂量的褪黑素治疗。
结果表明，MPTP 处理的小鼠表现出纹状体多巴胺水平降低，运动功能障碍和氧化应激增加。给予 L-多巴可改善小鼠的运动表现。褪黑素与 L-多巴联合治疗可改善对 L-多巴的运动反应，并增加纹状体多巴胺水平。这种组合降低了脂质过氧化，改善了还原型谷胱甘肽并提高了抗氧化酶活性（p≤0.05）。
总的来说，我们的研究表明褪黑素的抗氧化潜力使其成为治疗帕金森病的 L-多巴的有前途的候选药物。
