Biochemical and ultrastructural alterations in the rat ventral prostate due to repetitive alcohol drinking.
Previous studies showed that cytosolic and microsomal fractions from rat ventral prostate are able to biotransform ethanol to acetaldehyde and 1-hydroxyethyl radicals via xanthine oxidase and a non P450 dependent pathway respectively. Sprague Dawley male rats were fed with a Lieber and De Carli diet containing ethanol for 28 days and compared against adequately pair-fed controls. Prostate microsomal fractions were found to exhibit CYP2E1-mediated hydroxylase activity significantly lower than in the liver and it was induced by repetitive ethanol drinking. Ethanol drinking led to an increased susceptibility of prostatic lipids to oxidation, as detected by t-butylhydroperoxide-promoted chemiluminiscence emission and increased levels of lipid hydroperoxides (xylenol orange method). Ultrastructural alterations in the epithelial cells were observed. They consisted of marked condensation of chromatin around the perinuclear membrane, moderate dilatation of the endoplasmic reticulum and an increased number of epithelial cells undergoing apoptosis. The prostatic alcohol dehydrogenase activity of the stock rats was 4.84 times lower than that in the liver and aldehyde dehydrogenase activity in their microsomal, cytosolic and mitochondrial fractions was either not detectable or significantly less intense than in the liver. A single dose of ethanol led to significant acetaldehyde accumulation in the prostate. The results suggest that acetaldehyde accumulation in prostate tissue might result from both acetaldehyde produced in situ but also because of its low aldehyde dehydrogenase activity and its poor ability to metabolize acetaldehyde arriving via the blood. Acetaldehyde, 1-hydroxyethyl radical and the oxidative stress produced may lead to epithelial cell injury.
Gómez
M I Díaz
MI
Centro de Investigaciones Toxicológicas (CEITOX), CITEFA/CONICET, Juan B. de La Salle 4397, B1603ALO Villa Martelli, Buenos Aires, Argentina.
de Castro
C Rodríguez
CR
Fanelli
S L
SL
Quintans
L N
LN
Costantini
M H
MH
Castro
J A
JA
Castro
G D
GD
D000079:Acetaldehyde / Q000378:metabolism; D000284:Administration, Oral; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000428:Alcohol Drinking; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D018870:Endoplasmic Reticulum, Rough / Q000187:drug effects / Q000648:ultrastructure; D004847:Epithelial Cells / Q000187:drug effects / Q000648:ultrastructure; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008861:Microsomes / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009596:Nitrophenols / Q000378:metabolism; D011467:Prostate / Q000187:drug effects* / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D008054:Lipid Peroxides; D009596:Nitrophenols; D000431:Ethanol; D006899:Mixed Function Oxygenases; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde