Oxidative stress and pro-apoptotic conditions in a rodent model of Wilson's disease.
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.
Samuele
Alberta
A
Laboratory of Functional Neurochemistry, Neurological Institute "C. Mondino", Via Mondino, 2-27100 Pavia, Italy.
Mangiagalli
Anna
A
Armentero
Marie-Thérèse
MT
Fancellu
Roberto
R
Bazzini
Eleonora
E
Vairetti
Mariapia
M
Ferrigno
Andrea
A
Richelmi
Plinio
P
Nappi
Giuseppe
G
Blandini
Fabio
F
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
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