Mb. Kadiiska et Rp. Mason, Acute methanol intoxication generates free radicals in rats: An ESR spin trapping investigation, FREE RAD B, 28(7), 2000, pp. 1106-1114
Electron spin resonance (ESR) spectroscopy has been used to investigate fre
e radical generation in rats with acute methanol poisoning. The spin trappi
ng technique was used where a spin trapping agent, alpha-(4-pyridyl 1-oxide
)N-tert-butylnitrone (POBN), reacted with the corresponding alcohol-derived
or alcohol-dependent radical to from radical adducts. One radical adduct w
as detected in both bile and urine samples 2 h after acute methanol poisoni
ng in male Sprague Dawley rats. The hyperfine coupling constants for the ra
dical adduct from [C-13]-labeled methanol detected in the bile were a(N) =
15.58, a(beta)(H) = 2.81 G, and a(beta)(13C) = 4.53 G, which unambiguously
identified this species as POBN/(CH2OH)-C-.. The same radical adduct was de
tected in urine. The identification of a methanol-derived radical adduct in
samples from bile and urine provided strong direct evidence for the genera
tion of the alcohol-derived radicals during acute intoxication by methanol.
Simultaneous administration of the alcohol dehydrogenase inhibitor 4-methy
lpyrazole and methanol resulted in an increase in the generation of the fre
e radical metabolite detected in the bile. This is the first ESR evidence o
f methanol-derived free radical generation in an animal model of acute meth
anol intoxication. (C) 2000 Elsevier Science Inc.