Methods for depleting brain glutathione.
To search for a technique to deplete reduced glutathione (GSH) in brain, the influence of various types of compounds on brain GSH levels was investigated in mice. Of the compounds tested, cyclohexene-1-one, cycloheptene-1-one and diethyl maleate were shown to be potent GSH depletors in brain as well as in liver. The depletion of cerebral GSH ranged about 40-60% of control levels at 1 and 3 hr after intraperitoneal injection. Cyclohexene, cycloheptene, phorone, acetaminophen, and benzyl chloride caused mild depletion of cerebral GSH, but buthionine sulfoximine did not alter cerebral GSH levels. Further, intracerebroventricular injection of cyclohexene-1-one and cycloheptene-1-one caused depletion of brain GSH to about 60-80% of control levels at 1 hr after injection, and the effects persisted for at least 6 hr. Under these conditions, hepatic GSH was not altered. These results demonstrated that cyclohexene-1-one and cycloheptene-1-one can cause not only a marked depletion of brain GSH by systemic administration, but also depletion of cerebral GSH by intracerebroventricular injection by virtue of being water-soluble compounds. Thus, methods for depleting brain GSH employing both compounds are available for exploring possible functions of cerebral GSH in in vivo systems.
Masukawa
T
T
Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Sai
M
M
Tochino
Y
Y
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003508:Cycloheptanes / Q000008:administration & dosage / Q000494:pharmacology; D003512:Cyclohexanones / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism*; D007276:Injections, Intraventricular; D007659:Ketones / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008298:Maleates / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR
D003508:Cycloheptanes; D003512:Cyclohexanones; D007659:Ketones; D008298:Maleates; C025378:cyclohept-2-en-1-one; C028215:2-cyclohexen-1-one; C018637:phorone; C014476:diethyl maleate; D005978:Glutathione