[abstract] XANTHINE DEHYDROGENASE(XD) TO OXIDASE(XO) CONVERSION AND LIPID PEROXIDATION AFTER CO

Abstract

We have developed a rat model of CO poisoning, with a number of attributes consistent with clinical poisoning (JAP 68:997,1990). A biochemical index of brain injury, lipid peroxidation, can be identified 90 minutes following CO exposure, and this change is antagonized by treatment with 3 ATA 02, but not 1 ATA O2 (TAP 105:340, 1990). We now report that brain lipid peroxidation is due to O2 radicals generated by xanthine oxidase, and that the mechanism of action of hyperbaric oxygen is based on an antagonism of conversion of the nascent enzyme (XD) to the free radical-producing XO form. Involvement of XO was verified in tungsten-fed, XD+XO-depleted rats who had no detectable enzyme (units of activity=nmol isoxanthopterine/mg protein/min.), and no lipid peroxidation was noted 90 min. after CO poisoning, conjugated diene (CD) level= 0.087+0.005 (8). *=p<43.05, ANOVA. (table) CONTROL, IMMED.POST CO, 90 MIN POST CO, 90 MIN POST CO,1 ATA O2(&), 90 MIN POST CO, 3 ATA O2; XD+XO: 1.01+-0.10(6(#)), 1.05+-0.09(4), 0.99+-0.10(6), 1.10+-0.22(3), 0.95+-0.13(6); Total XO: 0.18+-0.02, 0.27+-0.04, 0.43+-0.06*, 0.39+-0.07*, 0.19+-0.05; Irrev.xo(+): 0.15+-0.04, 0.24+-0.02, 0.36+-0.06*, 0.38+-0.08*, 0.16+-0.06;cD($): 0.079+-.007, 0.080+-.005, 0.158+-.015*, 0.154+-0.020*, 0.078+-0.0005;(+)= tabsence of conversion to XD despite presence of 5mM dithioerythritol ($)= measure of lipid peroxidation(absorbance units 232 nm/mg lipid) (#)mean + S.E. (n), (&)= treatment given between 45 and 90 min. post-CO.