Oral pelargonidin exerts dose-dependent neuroprotection in 6-hydroxydopamine rat model of hemi-parkinsonism.
ABSTRACT Parkinson's disease (PD) is a neuropathological and debilitating disorder involving the degeneration of mesencephalic dopaminergic neurons. Neuroprotective effect of pelargonidin (Pel) has already been reported, therefore, this study examined whether Pel administration would attenuate behavioural and structural abnormalities and markers of oxidative stress in an experimental model of PD in rat. For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA, 12.5mug/5mul of saline-ascorbate)-lesioned rats were pre-treated p.o. with Pel (10 and/or 20mg/kg). Pel administration dose-dependently attenuated the rotational behavior in lesioned rats and protected the neurons of SNC against 6-OHDA toxicity. In addition, pre-treatment with Pel (20mg/kg) significantly decreased the 6-OHDA-induced thiobarbituric acid reactive substances (TBARS) formation, indicative of a neuroprotection against lipid peroxidation. Furthermore, the increase of nitrite levels induced by 6-OHDA, indicate the nitric oxide formation and free radicals production and the decrease of antioxidant defense enzyme superoxide dismutase (SOD) was non-significantly prevented by Pel (20mg/kg). In summary, Pel administration has a dose-dependent neuroprotective effect against 6-OHDA toxicity, partly through attenuating oxidative stress. Our findings suggest that pelargonidin could provide benefits, along with other therapies, in neurodegenerative disorders including PD.
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ABSTRACT: Mitochondrial oxidative stress (MOS) is a major factor in the underlying pathology of many neurodegenerative diseases. Here, we investigated the neuroprotective effects of a unique class of nutraceutical antioxidants, anthocyanins, against MOS-induced death of cultured cerebellar granule neurons (CGNs). Callistephin and kuromanin are anthocyanins derived from strawberries and black rice, respectively, whose neuroprotective properties have yet to be examined in detail. Glutathione (GSH)-sensitive MOS and intrinsic apoptosis were induced in CGNs by incubation with the Bcl-2 inhibitor, HA14-1. The effects of anthocyanin co-incubation on CGN survival were assessed. The anthocyanins demonstrated significant protection from MOS-induced apoptosis which was equivalent to that provided by the green tea polyphenol, epigallocatechin 3-gallate; however, neither anthocyanin was as effective as GSH at rescuing CGNs. Inhibition of Bcl-2 caused a significant reduction of mitochondrial GSH which was prevented by the anthocyanins. Furthermore, the anthocyanins inhibited iron-induced lipid peroxidation in rat brain homogenates and prevented cardiolipin oxidation induced by MOS in CGNs. MOS-induced mitochondrial fragmentation and proteolytic cleavage of the optic atrophy 1 (OPA1) fusion GTPase were also attenuated by the anthocyanins. Finally, the anthocyanins significantly enhanced GSH peroxidase activity in a cell-free assay. These data show that anthocyanins suppress MOS-induced apoptosis by preserving mitochondrial GSH and inhibiting cardiolipin oxidation and mitochondrial fragmentation. These nutraceutical antioxidants warrant further study as potential therapeutic agents for neurodegenerative diseases caused by MOS.Nutritional Neuroscience 11/2011; 14(6):249-59. DOI:10.1179/1476830511Y.0000000020 · 2.11 Impact Factor
- Oxidative Stress and Diseases, 04/2012; , ISBN: 978-953-51-0552-7
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ABSTRACT: For decades, it has been suggested that dysfunction of dopaminergic pathways and their associated modulations in dopamine levels play a major role in the pathogenesis of neurological disorders. Dopaminergic system is involved in the stress response, and the neural mechanisms involved in stress are important for current research, but the recent and past data on the stress response by dopaminergic system have received little attention. Therefore, we have discussed these data on the stress response and propose a role for dopamine in coping with stress. In addition, we have also discussed gastric stress ulcers and their correlation with dopaminergic system. Furthermore, we have also highlighted some of the glucocorticoids and dopamine-mediated neurological disorders. Our literature survey suggests that dopaminergic system has received little attention in both clinical and preclinical research on stress, but the current research on this issue will surely identify a better understanding of stressful events and will give better ideas for further efficient antistress treatments.Advances in Pharmacological Sciences 09/2012; 2012:182671. DOI:10.1155/2012/182671