Curcumin and an antioxidant formulation protect C57BL/6J mice from MPTP-induced Parkinson’s disease like changes: potential neuroprotection for neurodegeneration
Nov 9, 2018
Gladson Muthian,1 Veronica Mackey,1 Kedar Prasad,2 Clivel Charlton1
1Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, USA; 2Research and Development, Antioxidant Research Institute, Premier Micronutrient Corporation, Novato, CA, USA
Background: Degeneration of nigrostriatal (NS) dopamine (DA) neurons is the major neuropathological marker of Parkinson’s disease (PD). The cause for the disorder is unknown, but a prenatal sensitization stage and a postnatal precipitating stage may be involved. The sensitization stage is based on studies showing that prenatal exposure to low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) during the birth of substantia nigra (SN) DA neurons reduced DA, its metabolites, tyrosine hydroxylase (TH), the number of NS neurons as well as locomotor activities of the offspring. The observation that motor activities of the toxin-exposed animals deteriorated during aging, produced the condition equated to the precipitating stage. Other studies suggest that curcumin may offer protection. Purpose: For this project, we studied the protection offered by curcumin and an antioxidant formulation from MPTP-induced toxicity. Methods: Four groups of adult mice were pretreated, every other day for 27 days, with curcumin, 25 μg or 50 μg per mice of 25 g average body weight (equated to 1 mg/kg or 2 mg/kg) or with 25 mg/kg or 50 mg/kg of the antioxidant formulation. A control group received saline. MPTP was administer at the 20th day of pretreatment and all treatments continued for 7 days, then the animals were studied for changes in motor activities, striatal DA and DA metabolites as well as striatal and midbrain TH. The changes are indicative of PD-like NS damage. Results: The data showed that MPTP markedly reduced movements, as well as DA, its metabolites and TH. Curcumin and the antioxidant formulation blocked and ameliorated the toxic effects of MPTP. MPTP reduced DA to 49.1%. Curcumin restored DA to 87.3% and 84.8%, and the antioxidants restored and elevated DA to 132.1% and 121.2%. MPTP reduced striatal TH to 45.1%. The doses of curcumin restored TH to 60.9% and 75.1% and the antioxidants restored TH to 90.7% and 94.7%. Curcumin and the antioxidants reduced MPTP-induced death. Conclusion: The results demonstrated that curcumin and the antioxidants blocked the PD-like toxic effects of MPTP, indicative of the potentials as preventative measure for PD. Keywords: antioxidants, curcumin, dopamine, tyrosine hydroxylase, Parkinson’s disease
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