Linked Life Data

14675150

Source:http://linkedlifedata.com/resource/pubmed/id/14675150

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-12-16
pubmed:abstractText
In Guadeloupe, epidemiological data have linked atypical parkinsonism with fruit and herbal teas from plants of the Annonaceae family, particularly Annona muricata. These plants contain a class of powerful, lipophilic complex I inhibitors, the annonaceous acetogenins. To determine the neurotoxic potential of these substances, we administered annonacin, the major acetogenin of A. muricata, to rats intravenously with Azlet osmotic minipumps (3.8 and 7.6 mg per kg per day for 28 days). Annonacin inhibited complex I in brain homogenates in a concentration-dependent manner, and, when administered systemically, entered the brain parenchyma, where it was detected by matrix-associated laser desorption ionization-time of flight mass spectrometry, and decreased brain ATP levels by 44%. In the absence of evident systemic toxicity, we observed neuropathological abnormalities in the basal ganglia and brainstem nuclei. Stereological cell counts showed significant loss of dopaminergic neurones in the substantia nigra (-31.7%), and cholinergic (-37.9%) and dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32)-immunoreactive GABAergic neurones (-39.3%) in the striatum, accompanied by a significant increase in the number of astrocytes (35.4%) and microglial cells (73.4%). The distribution of the lesions was similar to that in patients with atypical parkinsonism. These data are compatible with the theory that annonaceous acetogenins, such as annonacin, might be implicated in the aetiology of Guadeloupean parkinsonism and support the hypothesis that some forms of parkinsonism might be induced by environmental toxins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
63-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14675150-Adenosine Triphosphate, pubmed-meshheading:14675150-Animals, pubmed-meshheading:14675150-Behavior, Animal, pubmed-meshheading:14675150-Cell Count, pubmed-meshheading:14675150-Corpus Striatum, pubmed-meshheading:14675150-Electron Transport Complex I, pubmed-meshheading:14675150-Furans, pubmed-meshheading:14675150-Gliosis, pubmed-meshheading:14675150-Guadeloupe, pubmed-meshheading:14675150-Infusions, Intravenous, pubmed-meshheading:14675150-Lactones, pubmed-meshheading:14675150-Male, pubmed-meshheading:14675150-Mitochondria, pubmed-meshheading:14675150-Neurodegenerative Diseases, pubmed-meshheading:14675150-Neurons, pubmed-meshheading:14675150-Parkinsonian Disorders, pubmed-meshheading:14675150-Plant Extracts, pubmed-meshheading:14675150-Rats, pubmed-meshheading:14675150-Rats, Inbred Lew, pubmed-meshheading:14675150-Substantia Nigra
pubmed:year
2004
pubmed:articleTitle
Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: possible relevance for atypical parkinsonism in Guadeloupe.
pubmed:affiliation
Experimental Neurology and Therapeutics, INSERM U289, Hôpital de la Salpêtrière, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't