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Synthesis of creatol, a hydroxyl radical adduct of creatinine and its increase by puromycin aminonucleoside in isolated rat hepatocytes
Author(s): Aoyagi K, Akiyama K, Kuzure Y, Takemura K, Nagase S, Ienaga K, Nakamura K, Koyama A, Narita M
Source: FREE RADICAL RESEARCH    Volume: 29    Issue: 3    Pages: 221-226    Published: 1998  
Times Cited: 7     References: 20     
Abstract: Creatol is a hydroxyl radical adduct of creatinine and the precursor of methylguanidine (MG), a uremic toxin. We investigate the synthesis of creatol and MG from creatinine and the effect of substances that affect the hydroxyl radical in isolated rat hepatocytes. In the presence of increasing concentrations of creatinine, rising level of creatol were found after 2 h incubation in Krebs-Henseleit bicarbonate buffer. However, further increase of creatol was not observed after 4 and 6 h incubations. On the other hand, MG after 2 h incubation achieved a level of about 50% that of creatol and increased depending on both the creatinine concentration and the incubation period. DMSO, a hydroxyl radical scavenger decreased the generation of creatol and MG by about 50% at 2.5 mM and the inhibition depended on DMSO concentration. Puromycin aminonucleoside (PAN) increased both by about 170%. These findings demonstrated that hepatocytes synthesize creatol prior to MG and are inhibited by a hydroxyl radical scavenger. They also show that PAN increased hydroxyl radical generation in tissue cells.
Document Type: Article
Language: English
Reprint Address: Aoyagi, K (reprint author), Univ Tsukuba, Inst Clin Med, Dept Internal Med, 1-1-1 Ten Nohdai, Tsukuba, Ibaraki 305 Japan
Addresses:
1. Univ Tsukuba, Inst Clin Med, Dept Internal Med, Tsukuba, Ibaraki 305 Japan
2. Nippon Zoki Pharmaceut Co Ltd, Inst Bioact Sci, Yashiro, Hyogo Japan
3. Mito Cent Hosp, Mito, Ibaraki Japan
Publisher: HARWOOD ACAD PUBL GMBH, C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL
Subject Category: Biochemistry & Molecular Biology
IDS Number: 129TR
ISSN: 1071-5762
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