Decreased tissue accumulation of 6-deoxy-6-[18F]fluoro-L-ascorbic acid in glutathione-deficient rats induced by administration of diethyl maleate.
The relationship between in vivo biodistribution of 6-deoxy-6-[18F]fluoro-L-ascorbic acid (18F-DFA) and the content of tissue glutathione (GSH) was investigated in Wistar male rats. Following intravenous administration of 18F-DFA, the accumulation of radioactivity in most tissues, including the adrenal glands, liver and brain, was significantly reduced together with a decrease in the content of GSH by preloading of diethyl maleate (DEM) which depletes cellular GSH. Similar decreased uptake was also observed in the distribution of L-[1-14C]ascorbic acid (14C-AA) after DEM treatment. The possible biological mechanisms, including competition with endogenous AA and ascorbate recycling, that modulate the uptake and accumulation into tissues of 18F-DFA and 14C-AA in GSH-deficient rats are discussed.
Yamamoto
Fumihiko
F
Faculty of Pharmaceutical Sciences, Kyushu University; Fukuoka 812-8582, Japan.
Kaneshiro
Tetsuo
T
Kato
Hiroharu
H
Mukai
Takahiro
T
Kuwabara
Yasuo
Y
Honda
Hiroshi
H
Maeda
Minoru
M
D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005978:Glutathione / Q000172:deficiency*; D008297:Male; D008298:Maleates / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D008298:Maleates; C076401:6-deoxy-6-fluoroascorbic acid; C014476:diethyl maleate; D005978:Glutathione; D001205:Ascorbic Acid