Ultrastructural and biochemical effects of repetitive ethanol administration on the rat ventral prostate

C. RODRIGUEZ DE CASTRO, G.D. CASTRO, M.I. DÍAZ GÓMEZ, A.M.A. DELGADO DE LAYÑO, M.H. COSTANTINI, FANELLI SL AND J.A. CASTRO

Fort Lauderdale, Florida,

Congreso; 26th Annual Meeting of the Research Society on Alcoholism and the 12th Congress of the International Society for Biomedical Research on Alcoholism.; 2003

International Society for Biomedical Research on Alcoholism

Previous studies from our laboratory evidenced that the rat ventral prostatic cytosolic (CYT) and microsomal (MIC) fractions biotransform ethanol (EtOH) to acetaldehyde (AC) and 1-hydroxyethyl free radicals (1HEt). In this work we report that rat prostate mitochondria (MIT) are also able to bioactivate EtOH to AC and 1 Het. The enzymatic process leading to AC requires oxygen but not NADH or NADPH, is fully inhibited by 1 mM diethyldithiocarbamate and is partially susceptible to 1mM desferrioxamina. Incubation mixtures containig the given subcellular fractions (CIT, MIC or MIT) and (if necessary) cofactors plus EtOH lead to covalent binding (CB) of the reactive metabolites formed to their NaBH4-reduced protein from the three fractions. Sprague Dawley male rats (starting at 125-150g) were fed with a nutritionally adequate liquid diet containing alcohol to provide 36% of total energy for 28 days (standard Lieber & De Carli rat diet, Dyets, Inc). This resulted in ultrastructurally visible alteration in their rat ventral prostate epithelial cells. They consisted of marked condensation of chreomatin around their perinuclear embrane and of moderate dilatation of their endoplasmic reticulum. We also observed that this repetitive EtOH adminstration was accompanied of slightly increased peroxidability of prostatic lipids as detectable by the t-butylhydroperoxide promoted chemiluminiscence emission test. In conclusio: rat ventral prostate has several metabolic pathways for EtOH bioactivation to AC and 1 HEt, some of which remain to be fully characterized. The reactive metabolites formed CB to cellular components and increased the peroxidability of their lipids. Both process might be involved in the cellular injury observed. The potential relevance of these findings to epidemiological studies available in literature in heavy alcohol drinkers might be of interest.