EFFECTS OF ETHANOL TREATMENT UPON SOURCES OXYGEN SPECIES IN BRAIN ANDLIVER

Sources of reactive oxygen species (ROS) generation have been compared in microsomal and mitochondrial fractions of brain and liver from eth anol-treated and control rats. Rates of ROS generation were quantitate d with the fluorescent probe precursor, 2'7'-dihydrochloroflurescin di acetate, whose validity has been previously established. The productio n of active pro-oxidant species was measured in the presence of variou s selective inhibitors of enzymes potentially able to contribute to ox idative events. Several steps in the arachidonic acid cascade appeared to constitute a large fraction of total ROS generating capacity. Chel ation of intrinsic iron with desferoxamine greatly reduced such capaci ty, especially in cerebral tissue. Aldehyde oxidases were active in ge nerating ROS in both tissues. Inhibition of catalase dramatically enha nced ROS in liver but not in brain microsomes. While no ethanol-treatm ent effects were found in brain, there was evidence that ethanol consu mption decreased hepatic levels of catalase, aldehyde oxidases and cyc looxygenase. However, despite these reductions, total basal ROS produc tion was elevated in liver but not brain fractions from treated animal s. The addition of an exogenous iron salt enhanced ROS formation to a lesser extent in ethanol-consuming rats than in controls. The elevatio n of basal hepatic ROS levels in ethanol-treated rats may thus be comp atible with the release of cytosolic low molecular weight free iron co mpounds into the cytosol.