Sodium cyanate alters glutathione homeostasis in rodent brain: relationship to neurodegenerative diseases in protein-deficient malnourished populations in Africa.

TitleSodium cyanate alters glutathione homeostasis in rodent brain: relationship to neurodegenerative diseases in protein-deficient malnourished populations in Africa.
Publication TypeJournal Article
Year of Publication1999
AuthorsTor-Agbidye J, Palmer VS, Spencer PS, Craig AM, Blythe LL, Sabri MI
JournalBrain research
Volume820
Issue1-2
Pagination12-9
Date Published1999 Feb 27
ISSN0006-8993
KeywordsAfrica, Animals, Brain, Cyanates, Female, Glutathione, Glutathione Disulfide, Glutathione Reductase, Homeostasis, Humans, Liver, Mice, Mice, Inbred Strains, Nerve Degeneration, Nutrition Disorders, Protein Deficiency, Rats, Rats, Sprague-Dawley, Time Factors, Tissue Distribution
Abstract

Sodium cyanate, a neurotoxic chemical in rodents, primates and humans, is implicated in neurodegenerative disorders in protein-deficient populations subsisting in parts of Africa on the cyanogenic plant cassava. The molecular and cellular mechanisms of cyanate neurotoxicity are not understood. This study investigates the effect of sodium cyanate on glutathione (GSH) homeostasis in rodent brain and liver in vitro and in vivo. GSH levels in mouse brain were rapidly, time- and dose-dependently decreased following intraperitoneal administration of 100, 200 or 300 mg/kg sodium cyanate. By contrast, GSH disulfide (GSSG) levels were increased and GSH/GSSG ratios were decreased in a dose-dependent manner in rat brain. Sodium cyanate depleted GSH levels in all regions of mouse brain. Brain glutathione reductase activity was dose-dependently inhibited, while glutathione peroxidase activity was not affected by sodium cyanate. The disruption of GSH homeotasis, as evidenced by reduced tissue GSH/GSSG ratios, likely results from cyanate-induced inhibition of glutathione reductase activity. The results of this study suggest that cyanate neurotoxicity, and perhaps cassava-associated neurodegenerative diseases, are mediated in part by disruption of glutathione homeostasis in neural tissue.

Alternate JournalBrain Res.