Mechanism involved in the ultrastructural and biochemical alterations on the rat ventral prostate due to repetitive ethanol administration

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

Mendoza,

Congreso; VI Congreso Latinoamericano de Mutagénesis Carcinogénesis Ambiental. XIV Congreso Argentino de Toxicología; 2005

Asociación Toxicológica Argentina

Previous studies from our laboratory showed that cytosolic and microsomal fractions from the rat ventral prostate are able to biotransform ethanol (EtOH) to acetaldehyde (AC) and 1-hydroxyethyl free radicals (1HEt). In this work we report that intact rat prostate mitochondria are also able to metabolize EtOH to AC and 1HEt via a rotenone-insensitive enzymatic process requiring oxygen and slightly but significantly enhanced by NADH and not by NADPH. The process is inhibited by 1mmol/L diethyldithiocarbamate, partially susceptible to 1 mmol/L deferoxamine and slightly increased by rotenone and diphenyleneiodonium chloride. Biochemical and ultrastructural studies were performed in Sprague Dawley rats fed with a nutritionally adequate liquid diet (Lieber & De Carli) containing EtOH for 28 days. An increased oxidability of prostatic lipids was observed by the t-butylhydroperoxide- promoted chemiluminiscence emission test and by the increased levels of lipid hydroperoxides, as evidenced by the xylenol orange procedure. Ultrastructural alterations in the epithelial cells were observed. They consisted of marked condensation of chromatin around the perinuclear membrane, moderate dilatation of their endoplasmic reticulum and some epithelial cells underwent apoptosis. In summary, past and present results show that the rat ventral prostate is able to metabolize EtOH to the toxic and reactive AC and 1HEt and to promote oxidative stress and lead to epithelial cell injury. Supported by grants from CONICET (PIP 02323) and UNSAM (PIDA UF013).