Reduction of brain glutathione by L-buthionine sulfoximine potentiates the dopamine-depleting action of 6-hydroxydopamine in rat striatum

J Neurochem. 1989 Mar;52(3):978-80. doi: 10.1111/j.1471-4159.1989.tb02550.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Buthionine Sulfoximine
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Drug Synergism
  • Glutathione / metabolism*
  • Hydroxydopamines / pharmacology*
  • Injections, Intraventricular
  • Male
  • Methionine Sulfoximine / administration & dosage
  • Methionine Sulfoximine / analogs & derivatives*
  • Methionine Sulfoximine / pharmacology
  • Norepinephrine / metabolism
  • Oxidation-Reduction
  • Oxidopamine
  • Rats
  • Rats, Inbred Strains

Substances

  • Hydroxydopamines
  • Methionine Sulfoximine
  • Buthionine Sulfoximine
  • Oxidopamine
  • Glutathione
  • Dopamine
  • Norepinephrine