METABOLISM OF ETHANOL TO ACETALDEHYDE AND INCREASED SUSCEPTIBILITY TO OXIDATIVE STRESS COULD PLAY A ROLE IN THE OVARIAN TISSUE CELL INJURY PROMOTED BY ALCOHOL DRINKING

M. FAUT; C. RODRÍGUEZ DE CASTRO; F. BIETTO; J.A. CASTRO; G.D. CASTRO

Helsinki

Congreso; The 12th Congress of European Society for Biomedical Research on Alcoholism; 2009

European Society for Biomedical Research on Alcoholism (ESBRA)

It is known that alcohol drinking can lead to reproductive problems in women. In this study we analyzed the possibility that part of those effects were mediated through alterations of ovarian function related to ethanol oxidation to acetaldehyde occurring in situ. We found that biotransformation in the rat ovary cytosolic fraction was partially inhibited by allopurinol, suggesting the participation of xanthine oxidoreductase in the process. The microsomal pathway was of enzymatic nature, requiring NADPH, sensitive to oxygen and significantly inhibited by sodium diethyldithiocarbamate, 4-methylpyrazole and diphenyleneiodonium. Histochemically, aldehyde dehydrogenase activity was detected in the ovarian tissue, in the strome surrounding the follicle while no alcohol dehydrogenase was detected. However, biochemical determination of alcohol dehydrogenase and aldehyde dehydrogenase activities in rat ovarian tissue revealed the presence of some activity of both enzymes but significantly lower than those found in the liver of the same animals. By repetitive exposure of animals to ethanol (standard Lieber & De Carli liquid diet for 28 days), the microsomal metabolism to acetaldehyde was increased but not in the case of the cytosolic fraction. In these animals, t-butylhydroperoxyde promoted chemiluminiscence was increased in comparison to control, revealing an increased susceptibility to oxidative stress due to alcohol drinking. Ultrastructure of ovarian tissue from rats treated with the standard Lieber & De Carli liquid diet revealed alterations at the level of the granulosa; theca interna and pellucida zones. In the secondary follicle, alterations consisted of marked condensation of chromatin attached to the nuclear inner membrane and this was particularly evident around nuclear pores. Intense dilatation of the outer perinuclear space could be observed. There was a marked dilatation of the rough endoplasmic reticulum accompanied of significant detachment of ribosomes from their membranes. Mitochondria appeared swollen. In the zona pellucida, most of cell processes from oocyte and corona radiata cells were absent or were broken totally or in part. Results suggest that in the rat ovary, metabolism of ethanol to acetaldehyde may play a role in alcohol effects on female reproductive function. Supported by ANPCyT (PICT 25354) and CONICET (PIP 5158).