Oxidation of alcohol to acetaldehyde, hydroxil radical formation, and oxidative stress in the rat uterus. Their reaction to reproductive toxicity

G CASTRO, L BUTHET, S FANELLI, C RODRIGUEZ DE CASTRO, M COSTANTINI, F BIETTO, J CASTRO

Barcelona

Congreso; XII International Congress of Toxicology (IUTOX); 2010

AETOX (Spanish Association of Toxicology) with the collaboration of EUROTOX

P208-005 Oxidation of alcohol to acetaldehyde, hydroxyl radical formation, and oxidative stress in the rat uterus. Their relation to reproductive toxicity G. Castro, L. Buthet, S. Fanelli, C. Rodriguez De Castro, M. Costantini, F. Bietto, J. Castro CITEFA-CONICET, Argentina It is known that alcohol drinking can lead to impairment in reproductive function in women. In this study we analyze the possibility that at least part of these effects were mediated through alterations of uterus function related to ethanol oxidation to acetaldehyde occurring in that tissue. We found that biotransformation in the cytosolic fraction is mediated by xanthine oxidoreductase (XOR), required a purine cosubstrate and was inhibited by allopurinol and pyrazol. By histochemistry XOR activity was detected in the epithelium and aldehyde dehydrogenase activity was detected in the muscular layer and the serosa. The microsomal process did not require NADPH but was of enzymatic nature, sensitive to oxygen and was inhibited by diethyldithiocarbamate, diphenyleneiodonium and partially by esculetin and nordihydroguaiaretic acid. Both, cytosolic and microsomal fractions from uterus showed the ability to generate hydroxyl radicals in the presence of alcohol, as detected by GC-MS of adducts formed with the spin trap PBN. Ultrastructure of uterus from rats treated with standard Lieber & De Carli liquid diet for 28 days revealed extensive vacuolization in cytoplasm and loss of cell content. In addition we observed the promotion of oxidative stress as evidenced by increased response in the t-butylhydroperoxide induced chemiluminiscence and the depletion of the protein sulfhydryl content. Results suggest that in the rat uterus, metabolism of ethanol to acetaldehyde may play a role in alcohol effects on female reproductive function. Acknowledgements: Supported by ANPCyT (PICT 2004 25354) and CONICET (PIP 5158). doi:10.1016/j.toxlet.2010.03.771