Effects of exogenous factors on the cerebral glutathione in rodents.
Since glutathione is thought to be involved in cerebral functions, changes in the glutathione level imply modulations of the neurotransmission in addition to all the known effects of GSH. It was investigated whether alterations of the cerebral glutathione can be induced by consumption of GSH, by inhibition or stimulation of the synthesis of GSH, or by an inhibition of the re-reduction of the oxidized glutathione. Aminophenazone, propyphenazone, acetaminophen, phenytoin, morphine and nitrofurantoin, known to deplete hepatic GSH, had no effects on cerebral GSH. Diethyl maleate (0.6 ml/kg) decreased the cerebral content of GSH and GSSG in adult rats as well as in fetuses. The depletion of the cerebral GSH caused by diethyl maleate treatment for 4 days was followed by an increase up to 125% and a subsequent return to the normal level after 1 week. In rats starved up to 71 h deficiency of exogenous amino acids caused only a minimal or no decrease in cerebral GSH. The specific inhibitor of the gamma-glutamylcysteine synthetase BSO only depleted GSH in the brain of young mice following the repeated s.c. administration of a high dose (890 mg/kg). After cobaltous chloride (20 mg/kg; twice a day for 2 or 4 days) the GSH level in the brain was unchanged. In vivo inhibition of the cerebral glutathione reductase was caused by ammonium metavanadate (12.5 mg/kg; three times a week for 6 weeks). Nitrofurantoin (150 mg/kg) had no effect. After lomustine (10 mg/kg) a minimal increase in glutathione reductase was found, but simultaneously also an increase in GSSG and of the ratio GSSG/total glutathione.
Bien
E
E
Institute of Pharmacology and Toxicology, Charité, Humboldt University Berlin, Federal Republic of Germany.
Vick
K
K
Skorka
G
G
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D005260:Female; D005978:Glutathione / Q000187:drug effects*; D005980:Glutathione Reductase / Q000378:metabolism; D008099:Liver / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D005980:Glutathione Reductase; D005978:Glutathione