EFFECTS OF ETHANOL TREATMENT UPON SOURCES OF REACTWE OXYGEN SPECIES IN BRAIN AND LIVER

Sources of reactive oxygen species (ROS) generation have beencompared in microsomal and niitochondrjal fractions of brainand liver from ethanol-treated and control rats. Rates of ROSgeneration were quantitated with the fluorescent probe precursor,2'7'-dihydrochloroflurescin diacetale, whose validity has beenpreviously established. The production of active pro-oxidantspecies was measured in the presence of various selective inhibitorsof enzymes potentially able to contribute to oxidative events.Several steps in the arachidonic acid cascade appeared to constitutea large fraction of total ROS generating capacity. Chelationof intrinsic iron with desferoxamine greatly reduced such capacity,especially in cerebral tissue. Aldehyde oxidascs were activein generating ROS in both tissues. Inhibition of catalase dramaticallyenhanced ROS in liver but not in brain microsomes. While noethanol-treatment effects were found in brain, there was evidencethat ethanol consumption decreased hepatic levels of catalase,aldehyde oxidases and cyclooxygenase. However, despite thesereductions, total basal ROS production was elevated in liverbut not brain fractions from treated animals. The addition ofan exogenous iron salt enhanced ROS formation to a lesser extentin ethanol-consuming rats than in controls. The elevation ofbasal hepatic ROS levels in ethanol-treated rats may thus becompatible with the release of cytosolic low molecular weightfree iron compounds into the cytosol.