Biochemical and ultrastructural alterations in the rat ventral prostate due to repetitive alcohol drinking

Abstract

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.

Testosterone Therapy Differently Regulates the Anti‐ and Pro‐Inflammatory Cytokines in the Plasma and Prostate of Rats Submitted to Chronic Ethanol Consumption (UChB)

“…34 In addition to the indirect effects caused by ethanol (e.g., decreasing plasma testosterone and triggering hormonal imbalance) 35,36 , some authors suggest a direct action based on the hypothesis that prostate is able to metabolizes ethanol to acetaldehyde which leads to the generation of free radicals and a subsequent oxidative stress in the organ. 37,38 The increased expression of NFR2 in the EtOH group seems to agree with the authors, because this transcription factor is a powerful redox sensor activated in response to oxidative stress. 39 In summary, our results suggest that ethanol differentially modulates the cytokines profile in the plasma and prostate microenvironment, being the prostate a local source of cytokines.…”

Rat ventral prostate xanthine oxidase–mediated metabolism of acetaldehyde to acetyl radical

“…8,9 More recently, our laboratory showed that rat ventral prostate microsomes exhibited some CYP2E1-mediated metabolic activity that was inducible by repetitive ethanol drinking. 10 However, rat prostate tissue evidenced to have very low ADh and AldDh activities. 10 Further, as a result of the own capacity to generate acetaldehyde and of the lack of ability to handle acetaldehyde either produced in situ or arriving from the liver or other tissues via blood, a significant accumulation of the aldehyde was observable.…”

“…10 However, rat prostate tissue evidenced to have very low ADh and AldDh activities. 10 Further, as a result of the own capacity to generate acetaldehyde and of the lack of ability to handle acetaldehyde either produced in situ or arriving from the liver or other tissues via blood, a significant accumulation of the aldehyde was observable. 10 The exposure of rat prostate tissue to repetitive ethanol drinking condition also led to oxidative stress production and to deleterious ultrastructural effects.…”

“…Further, evidence of an oxidative-stress response of prostate tissue after repetitive alcohol drinking was also anticipated. 10 In this study, we report that any acetaldehyde present in prostate tissue and known to accumulate to some extent there might be a source of additional free radicals of acetyl nature.…”

Alcohol Intake Increases High-grade Prostate Cancer Risk Among Men Taking Dutasteride in the REDUCE Trial

“…Acetaldehyde is a carcinogen that leads to the generation of reactive oxygen species (ROS) that promote lipid oxidation, DNA adducts, and DNA mutations [20]. ADH is also induced in the rat prostate in response to alcohol consumption [21], suggesting the possibility that alcohol may increase ROS directly in prostate tissue. DHT may also inhibit ADH [22] to slow alcohol metabolism and reduce ROS levels.…”