Metabolism of ethanol to acetaldehyde and increased susceptibility to oxidative stress could play a role in the ovarian tissue cell injury promoted by alcohol drinking

Abstract

It is known that drinking alcohol can lead to reproductive problems in women. In this study, we analyzed the possibility that part of those effects were mediated through alterations of ovarian function related to ethanol oxidation to acetaldehyde occurring in situ. Biotransformation in the rat ovary cytosolic fraction was partially inhibited by allopurinol, suggesting the participation of xanthine oxidoreductase in the process. Microsomal pathway was of enzymatic nature, requiring nicotinamide adenine dinucleotide phosphate-oxidase (NADPH), sensitive to oxygen and significantly inhibited by sodium diethyldithiocarbamate, 4-methylpyrazole and diphenyleneiodonium. Aldehyde dehydrogenase activity was detected by histochemistry in the ovarian tissue, in the strome surrounding the follicle while no alcohol dehydrogenase was detected. However, biochemical determination of alcohol dehydrogenase and aldehyde dehydrogenase activities in rat ovarian tissue revealed the presence of some activity of both enzymes but significantly lower than those found in the liver. By repetitive exposure of animals to ethanol, the microsomal metabolism to acetaldehyde was increased but not in the case of the cytosolic fraction. In these animals, t-butylhydroperoxyde-promoted chemiluminiscence was increased in comparison to control, revealing an increased susceptibility to oxidative stress due to alcohol drinking. Ultrastructure of ovarian tissue from rats exposed chronically to alcohol revealed alterations at the level of the granulosa; theca interna and pellucida zones. In the secondary follicle, alterations consisted of marked condensation of chromatin attached to the nuclear inner membrane. Intense dilatation of the outer perinuclear space could be observed. There was a marked dilatation of the rough endoplasmic reticulum accompanied of significant detachment of ribosomes from their membranes. Mitochondria appeared swollen. In the zona pellucida, most of the cell processes from oocyte and corona radiata cells were absent or broken totally or in part. Results suggest that in the rat ovary, metabolism of ethanol to acetaldehyde may play a role in alcohol effects on female reproductive function.

Effects of Alcohol on the Endocrine System

“…Long-term moderate alcohol consumption was also shown to decrease ovarian reserve which was associated with increased FSH levels 65 . Faut and colleagues 66 have suggested that an in-situ metabolism of ethanol to acetaldehyde increases the susceptibility of rat ovarian tissue to oxidative stress and leads to cell damage and ovarian dysfunction.…”

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.…”

Acetaldehyde Content and Oxidative Stress in the Deleterious Effects of Alcohol Drinking on Rat Uterine Horn

“…Ovarian and mammary tissues were already studied in more detail, and initial efforts directed to uterine horn were also performed [1, 23, 34, 35]. …”

“…Not all the effects of alcohol drinking in different target organs can be explained in terms of endocrine disturbances [12, 23, 36]. …”

“…Sections 1  µ m thick were stained with toluidine blue and examined with a light microscope in order to select epithelial areas for thin sectioning. Thin sections were cut with a diamond knife and mounted on copper grids (300 mesh), stained with uranyl acetate and lead citrate, and examined in a Philips EM300 transmission electron microscope [22, 23]. The microscopic observation of the uterine horn sections was carried out in a blinded fashion by two observers who were unaware of the treatment group.…”