Catalytic metalloporphyrin protects against MPTP-induced Parkinson's disease in mice

Abstract

Objective:To observe the effects of manganese(Ⅲ)meso-tetrakis(N,N'-diethylimidazolium-2-yl)porphyrin(MnTDM)in treatment of early Parkinson's disease(PD)mouse model induced by subcutaneous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)and to discuss its possible mechanism.Methods:Forty male C57BL/6 mice were evenly randomized into 4 groups:MPTP model group(subcutaneous injection of 25 mg/kg MPTP for 3 days).MnTDM +MPTP group(15 mg/kg MnTDM was subcutaneously injected 1 h before MPTP injection).MnTDM control group,and normal saline group.Performance of animals in the pole and swimming test was observed 3 days after the last injection.Levels of dopamine(DA)and its metabolites(3,4-dihydroxyphenylacetic acid [DOPAC] and homovanillic acid [HVA])in the striatum of animals were measured by high-performance liquid chromatography with an electrochemical detector(HPLC-ECD).Thiobarbituric acid(TBA)method was used to examine the levels of malondialdehyde(MDA).Results:Acute injection of MPTP could be used for establishment of PD model.The striatal levels of DA,DOPAC and HVA in MPTP group were significantly lower(P0.01)and the striatal level of MDA was significantly higher(P0.05)than those of the control group.MPTP had no obvious effect on the behavioral performance of the animals in a short term.MnTDM could partly inhibit the above effects of MPTP.Compared with MPTP group,MnTDM+MPTP group had significantly higher DA,DOPAC,and HVA levels and significantly lower MDA level(all P0.05).There was no significant difference in the behavioral indices of animals between the 4 groups.Conclusion:MnTDM can inhibit lipid peroxidation and promote DA production;it has preventive and therapeutic effects on MPTP-induced PD.