TY - JOUR
T1 - Sodium cyanate alters glutathione homeostasis in rodent brain
T2 - Relationship to neurodegenerative diseases in protein-deficient malnourished populations in Africa
AU - Tor-Agbidye, John
AU - Palmer, Valerie S.
AU - Spencer, Peter S.
AU - Craig, A. Morrie
AU - Blythe, Linda L.
AU - Sabri, Mohammad I.
PY - 1999/2/27
Y1 - 1999/2/27
N2 - 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 peurodegenerafive diseases, are mediated in part by disruption of glutathione homeostasis in neural tissue.
AB - 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 peurodegenerafive diseases, are mediated in part by disruption of glutathione homeostasis in neural tissue.
KW - GSH
KW - GSSG
KW - Glutathione homeostasis
KW - Glutathione peroxidase
KW - Glutathione reductase
KW - Neurodegenerative disease
KW - Neurotoxicity
KW - Sodium cyanate
UR - http://www.scopus.com/inward/record.url?scp=0033608458&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033608458&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(98)01343-2
DO - 10.1016/S0006-8993(98)01343-2
M3 - Article
C2 - 10023026
AN - SCOPUS:0033608458
VL - 820
SP - 12
EP - 19
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1-2
ER -