Reduction of brain glutathione by L-buthionine sulfoximine potentiates the dopamine-depleting action of 6-hydroxydopamine in rat striatum.
Sprague-Dawley rats were anesthetized with chloral hydrate, and plastic cannulae were permanently implanted into the lateral ventricles. The animals then were allowed to recover for 1-2 days. L-Buthionine sulfoximine (L-BSO), a selective inhibitor of glutathione (GSH) synthesis, and 6-hydroxydopamine (6-OH-DA), a selective catecholaminergic neurotoxin, were administered intracerebroventricularly. The striatal concentrations of GSH and monoamines were determined by HPLC with electrochemical detection. Two injections of L-BSO (3.2 mg, at a 48-h interval) resulted in a 70% reduction of striatal GSH. 6-OH-DA (150 or 300 micrograms) reduced the concentrations of striatal dopamine and noradrenaline 7 days after the administration, but left the concentrations of 5-hydroxytryptamine unaltered. L-BSO treatment did not produce any changes in the levels of monoamines per se but it potentiated the catecholamine-depleting effect of 6-OH-DA in the striatum. Thus, GSH appears to suppress the toxicity of 6-OH-DA, probably by scavenging the toxic species formed during 6-OH-DA oxidation. In view of these results one may suggest an important role for GSH in catecholaminergic neurons: protecting against the oxidation of endogenous catechols.
Pileblad
E
E
Department of Pharmacology, University of Göteborg, Sweden.
Magnusson
T
T
Fornstedt
B
B
D000818:Animals; D019328:Buthionine Sulfoximine; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism*; D006892:Hydroxydopamines / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D008717:Methionine Sulfoximine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010084:Oxidation-Reduction; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains
D006892:Hydroxydopamines; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D016627:Oxidopamine; D005978:Glutathione; D004298:Dopamine; D009638:Norepinephrine