Metabolism of ethanol to acetaldehyde by rat uterine horn subcellular fractions

Centro de Investigaciones Toxicológicas (CEITOX, CITEFA-CONICET) Juan B. de La Salle 4397, B1603ALO Villa Martelli, Argentina.
Human & Experimental Toxicology (Impact Factor: 1.75). 10/2011; 30(11):1785-94. DOI: 10.1177/0960327110396537
Source: PubMed


Controversial studies from others suggested that alcohol intake could be associated with some deleterious effects in the uterus. Not all the effects of alcohol drinking on female reproductive organs can be explained in terms of endocrine disturbances. Deleterious effect of alcohol or its metabolites in situ could also play a role. Accordingly, we found a metabolism of alcohol to acetaldehyde in the rat uterine horn tissue cytosolic fraction mediated by xanthine oxidoreductase, requiring a purine cosubstrate and inhibited by allopurinol. This activity was detected by histochemistry in the epithelium and aldehyde dehydrogenase activity was detected in the muscular layer and in the serosa. There was a microsomal process, not requiring NADPH and of enzymatic nature, oxygen-dependent and inhibited by diethyldithiocarbamate, diphenyleneiodonium and partially sensitive to esculetin and nordihydroguaiaretic acid. The presence of metabolic pathways in the uterine horn able to generate acetaldehyde, accompanied by a low capacity to destroy it through aldehyde dehydrogenase, led to acetaldehyde accumulation in the uterus during ethanol exposure. Results suggest that any acetaldehyde produced in situ or arriving to the uterine horn via blood would remain in this organ sufficiently to have the opportunity to react with critical molecules to cause deleterious effects.

6 Reads
  • Source
    • "The identified enzymes involved in acetaldehyde production included alcohol dehydrogenase (ADH) and xanthine oxidoreductase (XO) in the cytosolic fraction and the flavoenzyme NADPH oxidase and catalase in the microsomal fraction [1]. The ALDH activity present in the mitochondrial fraction was almost negligible and not detectable at all in the microsomal or cytosolic fraction. "
    [Show abstract] [Hide abstract]
    ABSTRACT: After alcohol exposure through a standard Lieber and De Carli diet for 28 days, a severe atrophy in the rat uteirne horn was observed, accompanied by significant alterations in its epithelial cells. Microsomal pathway of acetaldehyde production was slightly increased. Hydroxyl radicals were detected in the cytosolic fraction, and this was attributed to participation of xanthine oxidoreductase. They were also observed in the microsomal fraction in the presence of NADPH generating system. No generation of 1-hydroxyethyl was evidenced. The t -butylhydroperoxide-induced chemiluminescence analysis of uterine horn homogenates revealed a significant increase in the chemiluminiscence emission due to ethanol exposure. In the animals repeatedly exposed to alcohol, sulfhydryl content from uterine horn proteins was decreased, but no significant changes were observed in the protein carbonyl content from the same samples. Minor but significant decreasing changes were observed in the GSH content accompanied by a tendency to decrease in the GSH/GSSG ratio. A highly significant finding was the diminished activity content of glutathione peroxidase. Results suggest that acetaldehyde accumulation plus the oxidative stress may play an additional effect to the alcohol-promoted hormonal changes in the uterus reported by others after chronic exposure to alcohol.
    Journal of Toxicology 11/2013; 2013(3):161496. DOI:10.1155/2013/161496
  • [Show abstract] [Hide abstract]
    ABSTRACT: The role that organelle analysis has played in understanding biology is studied. Organelle analysis enables a more specific description of the molecular, biochemical, and physiological processes associated with diseases, embryonic development, tissue differentiation, organism aging, disease treatments, and organism response to pathogens. Confocal microscopy has become a routine tool for investigating subcellular organization, organelle networks, and organelle dynamics in cellular and tissue samples. Most organelles have a dynamic, three-dimensional (3D) organization inside the cell, which is tightly connected to their physiological functions. Due to this, a single 2D image inherently limits the information acquired about the distribution of a particular property within the organelle. The combination of subcellular fractionation with 'omic' technologies has become a powerful resource to characterize and catalogue the various subcellular environments in a cell.
    Chemical Reviews 04/2013; 113(4):2733-811. DOI:10.1021/cr300354g · 46.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Illegal alcohol beverages known as bogma raki in our country are consumed widely in our region. The studies investigating the relationship between alcohol consumption and hearing ability report different results. In this study, we aimed to investigate the toxic effects of bogma raki that contains neurotoxic substances on cochlea by electron microscopy. To the best of our knowledge, this study is the first in the literature. A total of 48 Wistar male albino rats (aged 12-16 weeks and weighing 200-240 g) were used in the study. The rats were divided into 4 groups with 12 animals in each group. The groups include control, bogma raki, walnut, and walnut + bogma raki groups. Bogma raki (30% v/v, 9.2 ml kg(-1) day(-1)) is added to drinking water of rats in bogma raki group (n = 12) for 4 weeks. Walnut group rats (n = 12) are fed with standard rat food and walnut without limitation (10 g kg(-1) day(-1)). Bogma raki + walnut group rats (n = 12) are fed with standard rat food and walnut and bogma raki is added to drinking water. The cochleas were dissected and removed en bloc and examined by electron microscopy. Perineuronal oedema around neurons of spiral ganglion and hairy cells of organ of Corti were present in the bogma raki group, walnut group and bogma raki + walnut group under electron microscopic examination. Comparing these three groups, there were no differences in the ultrastructural pathological changes. In the ultrastructural examination of the myelinated axons forming cochlear nerve, no ultrastructural pathology was detected in all the groups.
    Human &amp Experimental Toxicology 06/2014; 34(3). DOI:10.1177/0960327114537323 · 1.75 Impact Factor
Show more