K. Aoyagi et al., SYNTHESIS OF CREATOL, A HYDROXYL RADICAL ADDUCT OF CREATININE AND ITSINCREASE BY PUROMYCIN AMINONUCLEOSIDE IN ISOLATED RAT HEPATOCYTES, Free radical research (Print), 29(3), 1998, pp. 221-226
Creatol is a hydroxyl radical adduct of creatinine and the precursor o
f methylguanidine (MG), a uremic toxin. We investigate the synthesis o
f creatol and MG from creatinine and the effect of substances that aff
ect the hydroxyl radical in isolated rat hepatocytes. In the presence
of increasing concentrations of creatinine, rising level of creatol we
re found after 2 h incubation in Krebs-Henseleit bicarbonate buffer. H
owever, further increase of creatol was not observed after 4 and 6 h i
ncubations. On the other hand, MG after 2 h incubation achieved a leve
l of about 50% that of creatol and increased depending on both the cre
atinine concentration and the incubation period. DMSO, a hydroxyl radi
cal 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 de
monstrated that hepatocytes synthesize creatol prior to MG and are inh
ibited by a hydroxyl radical scavenger. They also show that PAN increa
sed hydroxyl radical generation in tissue cells.