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Glutathione deficiency potentiates manganese-induced increases in compounds associated with high-energy phosphate degradation in discrete brain areas of young and aged rats

Desole, Maria Speranza and Serra, Pier Andrea and Esposito, Giovanni and Delogu, Maria Rosaria and Migheli, Rossana and Fresu, Luigia Grazia and Rocchitta, Gaia Giovanna Maria and Miele, Maddalena (2000) Glutathione deficiency potentiates manganese-induced increases in compounds associated with high-energy phosphate degradation in discrete brain areas of young and aged rats. Aging, Vol. 12 (6), p. 470-477. ISSN 0394-9532. Article.

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Abstract

Aging is a factor known to increase neuronal vulnerability to oxidative stress, which is widely accepted as a mechanism of manganese-induced neuronal damage. We previously showed that subchronic exposure to manganese induced greater energy impairment (as revealed by increases in hypoxanthine, xanthine and uric acid levels) in the striatum and brainstem of aged rats vs young rats. This study shows that inhibition of glutathione (GSH) synthesis, by means of buthionine (SR) sulfoximine, decreased GSH levels and increased the ascorbic acid oxidation status in the striatum and limbic forebrain of both young and aged rats. In addition, inhibition of GSH synthesis greatly potentiated the manganese-induced increase in inosine, hypoxanthine, xanthine and uric acid levels in both regions of aged rats; moreover, inhibition of GSH synthesis significantly increased inosine, hypoxanthine, xanthine and uric acid levels in both regions of young rats, compared with the manganese-treated group. These results suggest that an impairment in the neuronal antioxidant system renders young rats susceptible to manganese-induced energetic impairment, and further support the hypothesis that an impairment in this system plays a permissive role in the increase of neuronal vulnerability that occurs with aging.

Item Type:Article
ID Code:5341
Status:Published
Refereed:Yes
Uncontrolled Keywords:Aging, glutathione deficiency, neuronal antioxidant system, neuronal vulnerability
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Divisions:001 Università di Sassari > 01 Dipartimenti > Neuroscienze, scienze materno infantili
Publisher:Editrice Kurtis
ISSN:0394-9532
Deposited On:24 Jan 2011 14:02

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