title: Experimental Parkinson's disease in monkeys. Effect of ergot alkaloid derivative on lipid peroxidation in different brain areas.
abstract: The effects of the Parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were evaluated in four different monkey brain areas (frontal and occipital cortex, caudate putamen, substantia nigra). The basal and stimulated lipid peroxidation and the reduced glutathione (GSH) concentration were evaluated in three groups of male Macaca fascicularis monkeys (6 animals/group): (a) controls; (b) MPTP-treated animals; (c) animals treated with MPTP and alpha-dihydroergocryptine (DEK; ergot alkaloid characterized by a dopaminergic agonist action). In MPTP-treated animals the GSH concentration was unchanged or decreased in a non-significant way in the frontal and occipital cortex, and in substantia nigra. The basal thiobabituric acid reactive substance (TBARS) concentrations were significantly higher in the caudate putamen and substantia nigra of MPTP-treated animals. In the MPTP-treated monkeys the DEK administration induced a restoration of basal TBARS values to nearly normal ones. By incubating tissue from different brain areas with FeSO4 plus ascorbic acid, the stimulation of lipid peroxidation decreased the TBARS production in the substantia nigra of the MPTP-treated animals. These results, taken together, may indicate that an increased lipid peroxidation could possibly play a role in producing the Parkinson-like syndrome by MPTP and that a free radical excess could be responsible for the degeneration of the substantia nigra. The treatment with an ergot alkaloid (i.e., alpha-dihydroergocryptine) partially antagonizes the MPTP-induced increase in basal TBARS concentration in caudate putamen.
authors.affiliation: Institute of Pharmacology, University of Pavia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Marzatico
authors.forename: C
authors.initials: C
authors.lastname: Café
authors.forename: M
authors.initials: M
authors.lastname: Taborelli
authors.forename: G
authors.initials: G
authors.lastname: Benzi
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D004088:Dihydroergotoxine / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D009778:Occipital Lobe / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D005296:Ferrous Compounds; D017392:Thiobarbituric Acid Reactive Substances; D004088:Dihydroergotoxine; C020748:ferrous sulfate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D005978:Glutathione; D001205:Ascorbic Acid