Aging Clinical and Experimental Research

, Volume 12, Issue 6, pp 470–477 | Cite as

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

  • M. S. Desole
  • P. A. Serra
  • G. Esposito
  • M. R. Delogu
  • R. Migheli
  • L. Fresu
  • G. Rocchitta
  • M. Miele
Original Article


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.

Key words

Aged rats brain glutathione deficiency manganese purine catabolism 


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Copyright information

© Springer Internal Publishing Switzerland 2000

Authors and Affiliations

  • M. S. Desole
    • 1
  • P. A. Serra
    • 1
  • G. Esposito
    • 1
  • M. R. Delogu
    • 1
  • R. Migheli
    • 1
  • L. Fresu
    • 1
  • G. Rocchitta
    • 1
  • M. Miele
    • 1
    • 2
  1. 1.Department of Pharmacology, Gynecology and Obstetrics, Faculty of MedicineUniversity of SassariSassariItaly
  2. 2.The Bethlem and Maudsley NHS TrustBethlem Royal HospitalBeckenham, KentUK

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