Antioxidant potential of melatonin enhances the response to L-dopa in 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-parkinsonian mice.

BACKGROUND 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. METHODS 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 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). CONCLUSIONS Overall, our study suggests that the antioxidant potential of melatonin makes it a promising candidate to L-dopa in treating Parkinson's disease.