Changes in oxidative stress in the rat brain during post-cardiac arrest reperfusion, and the effect of treatment with the free radical scavenger idebenone.

The study was designed to determine the effect of idebenone, an electron-trapping agent and free radical scavenger capable of crossing the blood-brain barrier, on cardiac arrest-induced oxidative brain stress. Stress indices used were the brain contents of thiobarbituric acid-reactive material (TBAR), conjugated dienes and protein and non-protein thiols. Twenty-four hours after receiving one oral dose of placebo or 100 mg kg(-1) idebenone, the rats were anaesthetized with diethyl ether and either decapitated immediately, or subjected to 7.5 min cardiac arrest induced by compression of the heart vessel bundle. The next groups of rats were sacrificed at the end of the cardiac arrest session, or resuscitated by external chest compression and artificial ventilation with air and sacrificed 15 min, 60 min, 24 h, and 72 h later while re-anesthetized with diethyl ether. Subsequent placebo or idebenone (100 mg kg(-1)) doses were given to the appropriate surviving rats once daily, beginning 8-10 min after the end of cardiac arrest session. Compared to pre-arrest values, TBAR and conjugated dienes' contents increased, respectively, by 339 and 286%, and protein and non-protein thiol contents decreased, respectively, by 69 and 85% within 60 min after the resuscitation in placebo-treated rats. Normalization of all oxidative stress indices in these rats was slow and incomplete even at 72 h. Idebenone treated rats showed no increase in TBAR contents, and a marked attenuation of changes in the other indices. These results show that oral idebenone greatly reduces oxidative brain stress following transient circulatory arrest in the rat. This effect could not be explained by simple stoichiometric scavenging of free radicals. Possible mechanisms of idebenone action are discussed.