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      The neuroprotective effect of Withania somnifera root extract in MPTP-intoxicated mice: An analysis of behavioral and biochemical varibles

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          Abstract

          We studied the influence of Withania somnifera (Ws) root extract (100 mg/kg body weight) on parkinsonism induced by 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP; i.p, 20 mg/kg body weight for 4 days), via the analysis of behavioral features and the oxidant-antioxidant imbalance in the midbrain of mice. A significant alteration in behavior, increased levels of thiobarbituric acid reactive substance (TBARS), and increased activities of superoxide dismutase (SOD) and catalase (CAT) were noticed in this region of brain in MPTP-treated mice. Oral treatment with the root extract resulted in a significant improvement in the mice’s behavoiur and antioxidant status, along with a significant reduction in the level of lipid peroxidation. The results indicated that at least part of the chronic stress-induced pathology may be due to oxidative stress, which is mitigated by Ws. Further studies are needed to assess the precise mechanism to support the clinical use of the plant as an antiparkinsonic drug.

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          A modified spectrophotometric assay of superoxide dismutase.

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            Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase.

            The neurotoxic chemical MPTP (1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine) is metabolized by rat brain mitochondrial fractions at a rate of 0.91 +/- 0.02 nmoles/mg protein/min. The major metabolite has been identified as the 1-methyl-4- phenylpyridinium species. This biotransformation process is blocked by 10(-7) M deprenyl and pargyline. MPTP itself inhibited the metabolism of benzylamine by brain mitochondrial fractions. These results are discussed in terms of possible bioactivation mechanisms that may be associated with the neurodegenerative properties of MPTP .
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              Increased levels of lipid hydroperoxides in the parkinsonian substantia nigra: an HPLC and ESR study.

              Previous studies examining the involvement of oxidative stress in the substantia nigra in Parkinson's disease have measured terminal products of lipid peroxidation or the function of antioxidant defense systems. We report a more specific early marker of lipid peroxidation, lipid hydroperoxides, in a high-performance liquid chromatography (HPLC) and electron spin resonance (ESR) investigation. HPLC-chemiluminescent detection revealed two classes of lipid hydroperoxides in brain tissue extracts--free fatty acid hydroperoxides and cholesterol lipid hydroperoxides. Only cholesterol lipid hydroperoxides were consistently detected in all tissue extracts. Cholesterol lipid hydroperoxides had a 10-fold increase in the Parkinson's disease substantia nigra compared to control subjects. ESR detection of radical degradation products, including those of lipid hydroperoxides, in nigral homogenates incubated with the spin trap N-t-butyl-alpha-phenyl nitrone (PBN) showed a marked variation in ESR signal between tissues. Despite the increased levels of lipid hydroperoxides in parkinsonian substantia nigra, there was no overall difference in ESR signal intensity between nigral tissues from controls and from patients with Parkinson's disease. The increased levels of an early component of the peroxidation chain in substantia nigra in Parkinson's disease support the hypothesis of a continuous toxic process involving oxygen radical activity. However, using previously frozen tissue, ESR evidence for increased radical formation could not be demonstrated.
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                Author and article information

                Contributors
                + 91-4144-239645 , + 91-4144-238145 , anatomysrs@yahoo.com
                Journal
                Cell Mol Biol Lett
                Cell. Mol. Biol. Lett
                Cellular & Molecular Biology Letters
                Versita (Warsaw )
                1425-8153
                1689-1392
                6 April 2007
                December 2007
                : 12
                : 4
                : 473-481
                Affiliations
                [1 ]GRID grid.411408.8, ISNI 0000000123697742, Department of Anatomy, Faculty of Medicine, , Annamalai University Annamalainagar, ; 608 002 India
                [2 ]GRID grid.411408.8, ISNI 0000000123697742, Department of Biochemistry and Biotechnology, Faculty of Science, , Annamalai University, ; Annamalainagar, 608 002 India
                [3 ]GRID grid.411408.8, ISNI 0000000123697742, Department of Surgery, Faculty of Medicine, , Annamalai University, ; Annamalainagar, 608 002 India
                Article
                15
                10.2478/s11658-007-0015-0
                6275882
                17415533
                c456a784-2578-4a1e-b5d1-1a952fa9f1c9
                © University of Wrocłlaw 2007
                History
                : 10 January 2007
                : 5 February 2007
                Categories
                Short Communication
                Custom metadata
                © University of Wrocław 2007

                mptp,withania somnifera,tbars,antioxidants,behaviour,midbrain
                mptp, withania somnifera, tbars, antioxidants, behaviour, midbrain

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