Journal of Pharmacology and Toxicology1816-496x2152-100xAcademic Journals Inc.10.3923/jpt.2006.418.428DizonMaria L.V.BrennanLisa A. M. BlackStephen 5200615Normal development of the Central Nervous System (CNS) requires a delicately timed sequence of neuronal proliferation, differentiation and remodeling. Ethanol exposure during gestation has been shown to perturb brain development. The mechanisms underlying this ethanol-induced toxicity are complex. Previous studies have indicated that ethanol exerts at least some of its neurotoxic effects via oxidative stress. Thus, we undertook a series of experiments to evaluate the role of oxidative stress in the toxic effects of ethanol on naive PC12 cells. In initial studies we evaluated whether Reactive Oxygen Species (ROS) were induced in PC12 cells exposed to increasing concentrations of ethanol. ROS levels in cells were quantitated using fluorescence microscopy and the superoxide sensitive dye, dihydroethidium. We then utilized adenovirus-mediated infection techniques to determine whether the over-expression of ROS scavengers, namely catalase, copper-zinc superoxide dismutatase (CuZnSOD) or manganese superoxide dismutatase (MnSOD), could protect PC12 cells from the cytotoxic effects of ethanol. The results obtained demonstrated a dose-dependent increase in ethidium positive cells in response to ethanol, indicating an increase in oxidative stress. In addition, PC12 cells over-expressing catalase, CuZnSOD and MnSOD were significantly protected from the cytotoxic effects of ethanol at concentrations greater than 50 mM as measured by cell viability assay. The level of protection afforded was greatest by MnSOD follwed by CuZnSOD and then catalase over-expression. We suggest that ethanol exerts its cytotoxic effects on PC12 cells by increasing mitochondrial superoxide production. Furthermore, we suggest that some of the neuronal cell death associated with Fetal Alcohol Syndrome (FAS) may be due to an increase in oxidative stress induced by ethanol metabolism.]]>Aebi, H.,19742121126Altura, B.M. and A. Gebrewold,1996220207210Armstead, W.M., R. Mirro, O.P. Thelin, M. Shibata and C.W. Leffler et al.,199223755762Beauchamp, C. and I. Fridovich,197144276287Bondy, S.C.,199263231241Chen, R.H., C. Sarnecki and J. Blenis,199212915927Coleman, W.B. and C.C. Cunningham,19901019142150Cragg, B. and S. Philips,1985325151160Davis, W.L., L.A. Crawford, O.J. Cooper, G.R. Farmer, D.L. Thomas and B.L. Freeman,1990in vitro.]]>10277293Devi, B.G., S. Schenker, B. Mazloum and G.I. Henderson,199613327332Dicker, E. and A.I. Cederbaum,1988229012906Dow, K.E. and R.J. Riopelle,198710330341Ferrer, I., E. Gaofre, I. Fabregues and D.L. Tejero,198978528532Greene, L.A. and A.S. Tischler,19767324242428Greene, L.A., J.M. Aletta, A. Rukenstein and S.H. Green,1987147207216Halliwell, B.,19925916091623Henderson, G.I., B.G. Devi, A. Perez and S. Schenker,199519714720Henderson, G.I., J.J. Chen and S. Schenker,19994D541D550Hoek, J.B. and E. Rubin,199025143156Jenkinson, P.C., D. Anderson and S.D. Gangolli,19866547554King, M.A., B.E. Hunter and D.W. Walker,1988459381385Kotch, L.E., S.Y. Chen and K.K. Sulik,199552128136Kotkoskie, L.A. and S. Norton,1988228579587Ledig, M., J.R. M'Paria and P. Mandel,19816385390Mariucci, G., M.V. Ambrosini, L. Colarieti and G. Bruschelli,199046753755Miller, M.W.,198622313081311Miller, M.W.,1987257372382Mitchell, J.J., M. Paiva and M.B. Heaton,199917163168Mochizuki, S. and A. Yoshida,198935431440Pentney, R.J. and A.P. Quackenbush,199014878886Pierce, D.R., D.C. Serbus and K.E. Light,19931712751280Ponsoda, X., R. Bort, R. Jover, M.J. Gomez-Lechon and J.V. Castell,19995815791585Rouach, H., M.K. Park, M.T. Orfanelli, B. Janvier and R. Nordmann,19871207211Sheehy, A.M., Y.T. Phung, K.R. Riemer and S.M. Black,1997527177Sun, A.Y., Y.M. Chen, M. James-Kracke, P. Wixom and Y. Cheng,19972211871192Tavares, M.A., M.M. Paula-Barbosa and B. Volk,198618725730Uysal, M., G. Kutalp, G. Ozdemirler and G. Aykac,198923227230Uysal, M., G. Ozdemirler, G. Kutalp and H. Oz,19899155158VanWinkle, W.B., M. Snuggs, J.C. Miller and L.M. Buja,199428119134Waltman, R. and E. Iniquez,197240180185Hammer, R.P., Jr.,19861986pp: 184-203pp: 184-203Rouach, H., P. Houze, M. Gentil, M.T. Orfanelli and R. Nordmann,199753539545