title: Pomegranate juice exacerbates oxidative stress and nigrostriatal degeneration in Parkinson's disease.
abstract: Numerous factors contribute to the death of substantia nigra (SN) dopamine (DA) neurons in Parkinson's disease (PD). Compelling evidence implicates mitochondrial deficiency, oxidative stress, and inflammation as important pathogenic factors in PD. Chronic exposure of rats to rotenone causes a PD-like syndrome, in part by causing oxidative damage and inflammation in substantia nigra. Pomegranate juice (PJ) has the greatest composite antioxidant potency index among beverages, and it has been demonstrated to have protective effects in a transgenic model of Alzheimer's disease. The present study was designed to examine the potential neuroprotective effects of PJ in the rotenone model of PD. Oral administration of PJ did not mitigate or prevent experimental PD but instead increased nigrostriatal terminal depletion, DA neuron loss, the inflammatory response, and caspase activation, thereby heightening neurodegeneration. The mechanisms underlying this effect are uncertain, but the finding that PJ per se enhanced nitrotyrosine, inducible nitric oxide synthase, and activated caspase-3 expression in nigral DA neurons is consistent with its potential pro-oxidant activity.
authors: Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA; Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Victor
authors: V
authors: Tapias
authors: School of Health Sciences, Purdue University, West Lafayette, IN, USA.
authors: Jason R
authors: JR
authors: Cannon
authors: Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA; Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA; Pittsburgh VA Healthcare System, Pittsburgh, PA, USA. Electronic address: jgreena@pitt.edu.
authors: J Timothy
authors: JT
authors: Greenamyre
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation; D029561:Lythraceae / Q000009:adverse effects*; D008297:Male; D028361:Mitochondrial Diseases; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010300:Parkinson Disease / Q000209:etiology* / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D012402:Rotenone; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D012402:Rotenone; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3
keywords: Inflammation; Mitochondria; Neuroprotection; Neurotoxicity; Oxidative stress; Parkinson's disease; Polyphenols; Pomegranate juice; Rotenone