title: Transport into brain of buthionine sulfoximine, an inhibitor of glutathione synthesis, is facilitated by esterification and administration of dimethylsulfoxide.
abstract: Buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, is poorly transported into the brain of adult mice, and only a slight decrease (approximately 10%) in the level of brain glutathione is found 30-60 min after intraperitoneal administration of BSO. When BSO is given as the ethyl ester, the brain level of BSO increases substantially after 5-15 min, and the glutathione level decreases by about 25% after 30-60 min. When BSO or its ester is given in 15% dimethylsulfoxide solution the brain levels of BSO are increased significantly and the brain glutathione levels are decreased by 20-35%. These observations suggest procedures that may be useful in decreasing the glutathione levels of the brains of adult animals. The finding that administration of BSO ethyl ester led to about a 25% decrease in the brain level of glutathione within 15 min suggests that a fraction of brain glutathione turns over very rapidly and may therefore be of special physiological significance.
authors.affiliation: Department of Biochemistry, Cornell University Medical College, New York, NY 10021.
authors.forename: R
authors.initials: R
authors.lastname: Steinherz
authors.forename: J
authors.initials: J
authors.lastname: Mårtensson
authors.forename: D
authors.initials: D
authors.lastname: Wellner
authors.forename: A
authors.initials: A
authors.lastname: Meister
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000378:metabolism; D019328:Buthionine Sulfoximine; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007700:Kinetics; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D051379:Mice
chemical_list: D000963:Antimetabolites; C065566:buthionine sulfoximine ethyl ester; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione; D004121:Dimethyl Sulfoxide