Ethylene glycol generates free radical metabolites in rats: An ESR in vivospin trapping investigation

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.