Effects of ethanol treatment upon sources of reactive oxygen species in brain and liver.
Sources of reactive oxygen species (ROS) generation have been compared in microsomal and mitochondrial fractions of brain and liver from ethanol-treated and control rats. Rates of ROS generation were quantitated with the fluorescent probe precursor, 2'7'-dihydrochloroflurescin diacetate, whose validity has been previously established. The production of active pro-oxidant species was measured in the presence of various selective inhibitors of enzymes potentially able to contribute to oxidative events. Several steps in the arachidonic acid cascade appeared to constitute a large fraction of total ROS generating capacity. Chelation of intrinsic iron with desferoxamine greatly reduced such capacity, especially in cerebral tissue. Aldehyde oxidases were active in generating ROS in both tissues. Inhibition of catalase dramatically enhanced ROS in liver but not in brain microsomes. While no ethanol-treatment effects were found in brain, there was evidence that ethanol consumption decreased hepatic levels of catalase, aldehyde oxidases and cyclooxygenase. However, despite these reductions, total basal ROS production was elevated in liver but not brain fractions from treated animals. The addition of an exogenous iron salt enhanced ROS formation to a lesser extent in ethanol-consuming rats than in controls. The elevation of basal hepatic ROS levels in ethanol-treated rats may thus be compatible with the release of cytosolic low molecular weight free iron compounds into the cytosol.
Bondy
S C
SC
Department of Community and Environmental Medicine, University of California at Irvine 92717.
Orozco
J
J
D000437:Alcoholism / Q000473:pathology / Q000534:rehabilitation*; D042931:Aldehyde Oxidase; D000445:Aldehyde Oxidoreductases / Q000502:physiology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D002374:Catalase / Q000502:physiology; D000431:Ethanol / Q000493:pharmacokinetics; D005609:Free Radicals; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000473:pathology*; D008297:Male; D009249:NADP / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
D005609:Free Radicals; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; D000431:Ethanol; D009249:NADP; D007501:Iron; D002374:Catalase; D011451:Prostaglandin-Endoperoxide Synthases; D000445:Aldehyde Oxidoreductases; D042931:Aldehyde Oxidase