Transport into brain of buthionine sulfoximine, an inhibitor of glutathione synthesis, is facilitated by esterification and administration of dimethylsulfoxide.
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.
Steinherz
R
R
Department of Biochemistry, Cornell University Medical College, New York, NY 10021.
Mårtensson
J
J
Wellner
D
D
Meister
A
A
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
D000963:Antimetabolites; C065566:buthionine sulfoximine ethyl ester; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione; D004121:Dimethyl Sulfoxide