Mb. Kadiiska et Rp. Mason, Ethylene glycol generates free radical metabolites in rats: An ESR in vivospin trapping investigation, CHEM RES T, 13(11), 2000, pp. 1187-1191
Ethylene glycol, best known as antifreeze, is most often ingested accidenta
lly or as a substitute for alcochol by chronic alcohol abusers. The toxicit
y of ethylene glycol poisoning is due to its toxic metabolites rather than
to ethylene glycol itself. In this study, electron spin resonance (ESR) spe
ctroscopy has been used to study free radical generation in rats by acute e
thylene glycol poisoning. The radical spin trapping technique was applied w
here the spin trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone
(POBN) reacted with free radical metabolites to form radical adducts in viv
o. The radical adducts from ethylene glycol intoxication were detected in b
oth the bile and urine samples of male Sprague-Dawley rats. The identificat
ion of the POBN-(.)[C-13]ethylene glycol radical adduct provides for the fi
rst time direct ESR evidence for the generation of the ethylene glycol-deri
ved radicals during acute intoxication by ethylene glycol, suggesting a new
metabolic pathway. Simultaneous administration of alcohol dehydrogenase in
hibitor 4-methylpyrazole with ethylene glycol resulted in an enhanced free
radical generation in the bile. This report is the first evidence of ethyle
ne glycol free radical metabolism in rats with acute ethylene glycol intoxi
cation.