title: Oxidative stress and pro-apoptotic conditions in a rodent model of Wilson's disease.
abstract: Wilson's disease (WD) is an inherited disorder, characterized by selective copper deposition in liver and brain, chronic hepatitis and extra-pyramidal signs. In this study, we investigated changes of biochemical markers of oxidative stress and apoptosis in liver, striatum and cerebral cortex homogenates from Long-Evans Cinnamon (LEC) rats, a mutant strain isolated from Long Evans (LE) rats, in whom spontaneous hepatitis develops shortly after birth. LEC and control (LE) rats at 11 and 14 weeks of age were used. We determined tissue levels of glutathione (GSH/GSSG ratio), lipid peroxides, protein-thiols (P-SH), nitric oxide metabolites, activities of caspase-3 and total superoxide-dismutase (SOD), striatal levels of monoamines and serum levels of hepatic amino-transferases. We observed a decrease of protein-thiols, GSH/GSSG ratio and nitrogen species associated to increased lipid peroxidation in the liver and striatum - but not in the cerebral cortex - of LEC rats, accompanied by dramatic increase in serum amino-transferases and decrease of striatal catecholamines. Conversely, SOD and caspase-3 activity increased consistently only in the cortex of LEC rats. Hence, we assume that enhanced oxidative stress may play a central role in the cell degeneration in WD, at the main sites of copper deposition, with discrete pro-apoptotic conditions developing in distal areas.
authors.affiliation: Laboratory of Functional Neurochemistry, Neurological Institute "C. Mondino", Via Mondino, 2-27100 Pavia, Italy.
authors.forename: Alberta
authors.initials: A
authors.lastname: Samuele
authors.forename: Anna
authors.initials: A
authors.lastname: Mangiagalli
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Armentero
authors.forename: Roberto
authors.initials: R
authors.lastname: Fancellu
authors.forename: Eleonora
authors.initials: E
authors.lastname: Bazzini
authors.forename: Mariapia
authors.initials: M
authors.lastname: Vairetti
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrigno
authors.forename: Plinio
authors.initials: P
authors.lastname: Richelmi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nappi
authors.forename: Fabio
authors.initials: F
authors.lastname: Blandini
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000378:metabolism; D006521:Hepatitis, Chronic / Q000209:etiology / Q000503:physiopathology*; D006527:Hepatolenticular Degeneration / Q000150:complications / Q000503:physiopathology*; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D020332:Rats, Inbred LEC; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances; D000637:Transaminases / Q000097:blood
chemical_list: D015306:Biogenic Monoamines; D008054:Lipid Peroxides; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D000637:Transaminases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione