Initial intraorgan formation of mercapturic acid.
The disposition of S-benzyl-glutathione (BSG) in male Wistar rats was evaluated by the HPLC method to examine whether the kidney and liver contributed independently to the biosynthesis of S-benzyl-N-acetylcysteine (BNAc), a mercapturic acid (Chart 1). After intravenous injection, BSG was rapidly transported in both the kidney and the liver at a ratio of about 7:3. Simultaneously, a large amount of BNAc was found in both the kidney and the liver. In the kidney, S-benzyl-cysteine (BCys) reached a maximum concentration (Cmax) at 2 min after BSG injection, whereas BNAc reached Cmax within 3 to 5 min. The generation of BNAc was also observed in the liver. While renal BNAc reached Cmax within 3 to 5 min, hepatic BNAc reached Cmax around 5 min after BSG injection. Moreover, the elimination half-life of the BNAc after intravenous injection of the BSG was equivalent to that observed after intravenous injection of the BNAc itself. These results demonstrate that the kidney contributes to the initial intraorgan generation of BNAc and that this mercapturic acid is also synthesized in the liver and preferentially excreted into urine.
Sano
K
K
Department of Drug Metabolism and Disposition, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan. ksano@my-pharm.ac.jp
Ikegami
Y
Y
Uesugi
T
T
D000111:Acetylcysteine / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004791:Enzyme Inhibitors / Q000032:analysis / Q000378:metabolism; D016166:Free Radical Scavengers / Q000032:analysis / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D007275:Injections, Intravenous; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; C045059:S-benzylglutathione; D005978:Glutathione; D000111:Acetylcysteine