Objective: This study aimed to investigate the effect of deferiprone on the striatal DA, oxidative stress and neuroinflammation markers as well as motor deficits in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice.

Background: Oxidative stress and neuroinflammation are central to the pathogenesis of Parkinson’s disease (PD) and striatal free iron is a contributor. Deferiprone (DFP) is a potent iron chelator with promise for treating PD. However, data on the effects of this chelator on striatal dopamine (DA), oxidative stress, neuroinflammation markers, and various motor deficits in different neurotoxin models of PD are still limited.

Method: Four groups of mice (6 per group) were used for the study. Group 1 (control) received only distilled water. Group 2 received MPTP (10 mg/kg i.p) for 21 days, in addition to this, Group 3 received Carbidopa-Levodopa (CD-LP) (25/100 mg/kg p.o) while Group 4 received DFP (75 mg/kg p.o). Motor functions were assessed using catalepsy bar test (CBT), open field test (OFT) and beam walk test (BWT). The striatal DA, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) concentrations were determined using ELISA. Reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and malondialdhyde (MDA) were also analyzed using assay kits.

Results: Both CD-LP and DFP reversed the DA, neuroinflammation and oxidative stress markers significantly close to the levels seen in the controls. While the effect of CD-LP was more significant on the DA compared to DFP, the latter had more significant effects on the neuroinflammation and oxidative stress markers. In the CBT, the mean time of maintaining posture was significantly (p<0.01) reduced in the treated groups although more significant reduction was seen in the CD-LD group compared to the DFP group. Both CD-LD and DFP significantly (p<0.01) reduced time to cross the beam and number of foot slips in the BWT to similar extents. The total distance travelled, rearing frequency and time spent in center in the OFT were reversed by CD-LD and DFP treatments.

Conclusion: Deferiprone increased striatal DA concentration, reduces neuroinflammation, oxidative stress and improved motor functions in an MPTP mice model of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/deferiprone-improves-striatal-dopamine-by-reducing-neuroinflammation-and-oxidative-stress-in-mptp-induced-mice-model-of-parkinsons-disease/