Acetaldehyde accumulation in rat mammary tissue after an acute treatment with alcohol

Abstract

Previous studies reported the presence in rat mammary tissue of a cytosolic xanthine oxidoreductase pathway for the metabolism of alcohol to acetaldehyde and hydroxyl radicals and to the microsomal biotransformation of ethanol to acetaldehyde. It was also reported that after chronic ethanol drinking stressful oxidative conditions can be observed. The present work reports that even after single doses of ethanol, given at three different levels (6.3 g kg(-1); 3.8 g kg(-1) or 0.6 g kg(-1) p.o.), acetaldehyde accumulates for prolonged periods of time in the mammary tissue to reach concentrations higher than in blood (e.g. 5.1+/-1.2 nmol g(-1) versus 0.2+/-0.1 nmol ml(-1), for 6.3 g kg(-1) dose, 6 h after intoxication). The presence in rat mammary tissue of low activities of additional enzymes able to generate acetaldehyde was established (alcohol dehydrogenase: 0.97+/-0.84 mU mg(-1) protein; CYP2E1: 1.30+/-0.12 x 10(-2) pmol 4-nitrocatechol min(-1) mg(-1) protein) and a low activity of aldehyde dehydrogenase was observed in the cytosolic, mitochondrial and microsomal fractions (0.02+/-0.04; 0.35+/-0.09 and 0.72+/-0.19 mU mg(-1) protein, respectively). After a single high dose of ethanol, an increased susceptibility to oxidative stress was observed, as evidenced by changes in the shape of t-butylhydroperoxide induced emission of chemiluminescence in mammary tissue (6.3 g kg(-1) dose; at 3 and 6 h). In summary, the results show that even after single doses of ethanol, acetaldehyde, either formed in situ or arriving via blood, tends to accumulate in mammary tissue and that this condition might decrease cell defenses against injury.

Alcohol Use and Breast Cancer: A Critical Review

“…Alcohol dehydrogenase (ADH) metabolizes EtOH into acetaldehyde, its primary carcinogenic metabolite (Secretan et al, 2009) in breast cancer cells where it accumulates within mammary tissues following alcohol consumption (Castro et al, 2008). Using human cell, animal cell, and in vitro models, acetaldehyde was observed to form DNA adducts (Rintala et al, 2000;Vaca et al, 1998).…”

Links between Alcohol Consumption and Breast Cancer: A Look at the Evidence

“…In rats, acetalde-hyde accumulates in mammary tissue for prolonged periods of time after a single oral dose of ethanol and finally reaches a level considerably higher than in blood [115,116]. This is primarily due to increasing production of acetaldehyde in mammary tissue, the limited ability to detoxify acetaldehyde in mammary tissue and acetaldehyde produced elsewhere and delivered to mammary tissue via blood [108].…”

Calcium Channels and Oxidative Stress Mediate a Synergistic Disruption of Tight Junctions by Ethanol and Acetaldehyde in Caco-2 Cell Monolayers

“…Tissues in vivo are simultaneously exposed to ethanol and acetaldehyde due to ubiquitous distribution of alcohol dehydrogenase (ADH)3, CYP2E14 and catalase56, all known to metabolize ethanol into acetaldehyde. Mounting evidence indicates that ethanol metabolism by ADH into acetaldehyde plays a crucial role in alcoholic tissue injury in many organs78910111213. Studies reported so far have evaluated the effect of either ethanol or acetaldehyde on tissue functions, including the epithelial barrier function.…”