scholarly journals Ethanol exposure during late gestation and nursing in the rat: Effects upon maternal care, ethanol metabolism and infantile milk intake

2008 ◽  
Vol 91 (1) ◽  
pp. 21-31 ◽  
Author(s):  
M PUETA ◽  
P ABATE ◽  
O HAYMAL ◽  
N SPEAR ◽  
J MOLINA
Keyword(s):  
Maternal Care ◽  
Ethanol Exposure ◽  
Milk Intake ◽  
Late Gestation ◽  
Ethanol Metabolism

scholarly journals Acute ethanol exposure disrupts VEGF receptor cell signaling in endothelial cells

2008 ◽  
Vol 295 (1) ◽  
pp. H174-H184 ◽  
Author(s):  
Katherine A. Radek ◽  
Elizabeth J. Kovacs ◽  
Richard L. Gallo ◽  
Luisa A. DiPietro
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Signaling ◽  
Network Formation ◽  
Ethanol Exposure ◽  
Capillary Network ◽  
Ethanol Metabolism ◽  
Vegf Receptor ◽  
Acute Ethanol

Physiological angiogenesis is regulated by various factors, including signaling through vascular endothelial growth factor (VEGF) receptors. We previously reported that a single dose of ethanol (1.4 g/kg), yielding a blood alcohol concentration of 100 mg/dl, significantly impairs angiogenesis in murine wounds, despite adequate levels of VEGF, suggesting direct effects of ethanol on endothelial cell signaling (40). To examine the mechanism by which ethanol influences angiogenesis in wounds, we employed two different in vitro angiogenesis assays to determine whether acute ethanol exposure (100 mg/dl) would have long-lasting effects on VEGF-induced capillary network formation. Ethanol exposure resulted in reduced VEGF-induced cord formation on collagen and reduced capillary network structure on Matrigel in vitro. In addition, ethanol exposure decreased expression of endothelial VEGF receptor-2, as well as VEGF receptor-2 phosphorylation in vitro. Inhibition of ethanol metabolism by 4-methylpyrazole partially abrogated the effect of ethanol on endothelial cell cord formation. However, mice treated with t-butanol, an alcohol not metabolized by alcohol dehydrogenase, exhibited no change in wound vascularity. These results suggest that products of ethanol metabolism are important factors in the development of ethanol-induced changes in endothelial cell responsiveness to VEGF. In vivo, ethanol exposure caused both decreased angiogenesis and increased hypoxia in wounds. Moreover, in vitro experiments demonstrated a direct effect of ethanol on the response to hypoxia in endothelial cells, as ethanol diminished nuclear hypoxia-inducible factor-1α protein levels. Together, the data establish that acute ethanol exposure significantly impairs angiogenesis and suggest that this effect is mediated by changes in endothelial cell responsiveness to both VEGF and hypoxia.

scholarly journals Can low-level ethanol exposure during pregnancy influence maternal care? An investigation using two strains of rat across two generations

2015 ◽  
Vol 148 ◽  
pp. 111-121 ◽  
Author(s):  
Daniel O. Popoola ◽  
Amanda P. Borrow ◽  
Julia E. Sanders ◽  
Michael E. Nizhnikov ◽  
Nicole M. Cameron
Keyword(s):  
Maternal Care ◽  
Ethanol Exposure ◽  
Low Level ◽  
Two Generations ◽  
Exposure During Pregnancy

scholarly journals Acetaldehyde accelerates HCV-induced impairment of innate immunity by suppressing methylation reactions in liver cells

2015 ◽  
Vol 309 (7) ◽  
pp. G566-G577 ◽  
Author(s):  
Murali Ganesan ◽  
Jinjin Zhang ◽  
Tatiana Bronich ◽  
Larisa I. Poluektova ◽  
Terrence M. Donohue ◽  
...  
Keyword(s):  
Alcohol Exposure ◽  
Liver Cells ◽  
Ethanol Exposure ◽  
Ethanol Metabolism ◽  
In Vivo Studies ◽  
Temporary Increase ◽  
Hcv Rna ◽  
Induced Apoptosis ◽  
Induced Defects

Alcohol exposure worsens the course and outcomes of hepatitis C virus (HCV) infection. Activation of protective antiviral genes is induced by IFN-α signaling, which is altered in liver cells by either HCV or ethanol exposure. However, the mechanisms of the combined effects of HCV and ethanol metabolism in IFN-α signaling modulation are not well elucidated. Here, we explored a possibility that ethanol metabolism potentiates HCV-mediated dysregulation of IFN-α signaling in liver cells via impairment of methylation reactions. HCV-infected Huh7.5 CYP2E1+ cells and human hepatocytes were exposed to acetaldehyde (Ach)-generating system (AGS) and stimulated with IFN-α to activate IFN-sensitive genes (ISG) via the Jak-STAT-1 pathway. We observed significant suppression of signaling events by Ach. Ach exposure decreased STAT-1 methylation via activation of protein phosphatase 2A and increased the protein inhibitor of activated STAT-1 (PIAS-1)-STAT-1 complex formation in both HCV+ and HCV− cells, preventing ISG activation. Treatment with a promethylating agent, betaine, attenuated all examined Ach-induced defects. Ethanol metabolism-induced changes in ISGs are methylation related and confirmed by in vivo studies on HCV+ transgenic mice. HCV- and Ach-induced impairment of IFN signaling temporarily increased HCV RNA levels followed by apoptosis of heavily infected cells. We concluded that Ach potentiates the suppressive effects of HCV on activation of ISGs attributable to methylation-dependent dysregulation of IFN-α signaling. A temporary increase in HCV RNA sensitizes the liver cells to Ach-induced apoptosis. Betaine reverses the inhibitory effects of Ach on IFN signaling and thus can be used for treatment of HCV+ alcohol-abusing patients.

scholarly journals Acetaldehyde-Mediated Neurotoxicity: Relevance to Fetal Alcohol Spectrum Disorders

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Ming Tong ◽  
Lisa Longato ◽  
Quynh-GiaoLy Nguyen ◽  
William C. Chen ◽  
Amy Spaisman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Alcohol Exposure ◽  
Ethanol Exposure ◽  
Ethanol Metabolism ◽  
Toxic Metabolite ◽  
Prenatal Ethanol Exposure ◽  
Impaired Insulin ◽  
Insulin Responsiveness ◽  
Igf Signaling

Ethanol-induced neuro-developmental abnormalities are associated with impaired insulin and IGF signaling, and increased oxidative stress in CNS neurons. We examined the roles of ethanol and its principal toxic metabolite, acetaldehyde, as mediators of impaired insulin/IGF signaling and oxidative injury in immature cerebellar neurons. Cultures were exposed to 3.5 mM acetaldehyde or 50 mM ethanol ± 4-methylpyrazole (4-MP), an inhibitor of ethanol metabolism, and viability, mitochondrial function, oxidative stress, DNA damage, and insulin responsiveness were measured 48 hours later. Acetaldehyde or ethanol increased neuronal death and levels of 8-OHdG and 4-HNE, and reduced mitochondrial function. Ethanol inhibited insulin responsiveness, whereas acetaldehyde did not. 4-MP abated ethanol-induced oxidative stress and mitochondrial dysfunction, but failed to restore insulin responsiveness. Furthermore, alcohol and aldehyde metabolizing enzyme genes were inhibited by prenatal ethanol exposure; this effect was mediated by acetaldehyde and not ethanol + 4MP. These findings suggest that brain insulin resistance in prenatal alcohol exposure is caused by direct effects of ethanol, whereas oxidative stress induced neuronal injury is likely mediated by ethanol and its toxic metabolites. Moreover, the adverse effects of prenatal ethanol exposure on brain development may be exacerbated by down-regulation of genes needed for metabolism and detoxification of alcohol in the brain.

Chronic ethanol exposure during late gestation produces behavioral anomalies in neonatal lambs

2000 ◽  
Vol 22 (2) ◽  
pp. 205-212 ◽  
Author(s):  
Jennifer Spear-Smith ◽  
James F. Brien ◽  
Marjorie Grafe ◽  
Richard Allrich ◽  
James D. Reynolds
Keyword(s):  
Ethanol Exposure ◽  
Chronic Ethanol ◽  
Late Gestation ◽  
Chronic Ethanol Exposure ◽  
Neonatal Lambs

Prostaglandin E2 inhibition of fetal breathing movements is not sustained during prolonged reduced uterine blood flow in sheep

1998 ◽  
Vol 76 (9) ◽  
pp. 858-866 ◽  
Author(s):  
Carole S Watson ◽  
Jacobus H Homan ◽  
Susan E White ◽  
John R Challis ◽  
Alan D Bocking
Keyword(s):  
Blood Flow ◽  
Ethanol Exposure ◽  
Late Gestation ◽  
Prostaglandin E ◽  
Uterine Blood Flow ◽  
Fetal Plasma ◽  
Fetal Breathing ◽  
Fetal Breathing Movements ◽  
Baseline Incidence ◽  
And Control

Fetal breathing movements (FBM) are inhibited by both exogenous prostaglandin E2 (PGE2) and ethanol in sheep. Maternal ethanol exposure in late-gestation sheep also increases fetal [PGE2]. However, during prolonged reduced uterine blood flow (RUBF) when [PGE2] in fetal plasma is already elevated, FBM are not inhibited by ethanol. These experiments were designed, therefore, to test the hypothesis that the FBM response to PGE2 is also diminished during RUBF. PGE2 (594 ± 19 ng·min-1·kg-1 fetal body weight) was infused for 6 h into the jugular vein of RUBF (PO2 = 14 ± 1 mmHg (1 mmHg = 133.3 Pa); n = 7) and control (PO2 = 22 ± 1 mmHg (p < 0.01); n = 7) ovine fetuses, and the effect on FBM, electrocortical (ECoG), and electroocular activities was determined. The infusion of PGE2 increased plasma [PGE2] from 881 ± 162 to 1189 ± 114 pg·mL-1 in RUBF fetuses and from 334 ± 72 to 616 ± 118 pg·mL-1 (p < 0.05) in control fetuses. FBM were initially inhibited by PGE2 from 22.5 ± 9.4 and 17.9 ± 6.5% of the time to 6.9 ± 2.4 and 0.5 ± 0.4% (p < 0.01) in RUBF and control fetuses, respectively. FBM remained inhibited in control fetuses throughout the infusion but returned to baseline incidence in RUBF fetuses in the last 2 h of the infusion. These results are consistent with the hypothesis that one component of the adaptative mechanisms of the fetus to prolonged RUBF is an altered response of FBM to exogenous PGE2. We speculate that the lack of a sustained inhibition in FBM during RUBF with infusion of PGE2 may be a result of an alteration in brainstem receptor function or number or local PGE2 removal.Key words: fetal breathing movements, prostaglandin E2, hypoxia, reduced uterine blood flow, ethanol, fetal behaviour.

scholarly journals Genetic evidence of widespread variation in ethanol metabolism among mammals: revisiting the ‘myth' of natural intoxication

2020 ◽  
Vol 16 (4) ◽  
pp. 20200070 ◽  
Author(s):  
Mareike C. Janiak ◽  
Swellan L. Pinto ◽  
Gwen Duytschaever ◽  
Matthew A. Carrigan ◽  
Amanda D. Melin
Keyword(s):  
Evolutionary History ◽  
Evolutionary Relationship ◽  
Ethanol Exposure ◽  
Anthropogenic Sources ◽  
Ethanol Metabolism ◽  
Last Common Ancestor ◽  
Dietary Adaptation ◽  
Metabolic Adaptations ◽  
Comparative Genetic Analysis ◽  
Insight Into

Humans have a long evolutionary relationship with ethanol, pre-dating anthropogenic sources, and possess unusually efficient ethanol metabolism, through a mutation that evolved in our last common ancestor with African great apes. Increased exposure to dietary ethanol through fermenting fruits and nectars is hypothesized to have selected for this in our lineage. Yet, other mammals have frugivorous and nectarivorous diets, raising the possibility of natural ethanol exposure and adaptation in other taxa. We conduct a comparative genetic analysis of alcohol dehydrogenase class IV (ADH IV) across mammals to provide insight into their evolutionary history with ethanol. We find genetic variation and multiple pseudogenization events in ADH IV, indicating the ability to metabolize ethanol is variable. We suggest that ADH enzymes are evolutionarily plastic and show promise for revealing dietary adaptation. We further highlight the derived condition of humans and draw attention to problems with modelling the physiological responses of other mammals on them, a practice that has led to potentially erroneous conclusions about the likelihood of natural intoxication in wild animals. It is a fallacy to assume that other animals share our metabolic adaptations, rather than taking into consideration each species' unique physiology.

scholarly journals Tributyrin Supplementation Protects Immune Responses and Vasculature and Reduces Oxidative Stress in the Proximal Colon of Mice Exposed to Chronic-Binge Ethanol Feeding

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
B. Glueck ◽  
Y. Han ◽  
G. A. M. Cresci
Keyword(s):  
Oxidative Stress ◽  
Immune Responses ◽  
Immune Function ◽  
Proximal Colon ◽  
Ethanol Exposure ◽  
The Body ◽  
Ethanol Metabolism ◽  
Gut Dysbiosis ◽  
Binge Ethanol Exposure ◽  
Binge Ethanol

Excessive ethanol consumption causes adverse effects and contributes to organ dysfunction. Ethanol metabolism triggers oxidative stress, altered immune function, and gut dysbiosis. The gut microbiome is known to contribute to the maintenance of intestinal homeostasis, and disturbances are associated with pathology. A consequence of gut dysbiosis is also alterations in its metabolic and fermentation byproducts. The gut microbiota ferments undigested dietary polysaccharides to yield short-chain fatty acids, predominantly acetate, propionate, and butyrate. Butyrate has many biological mechanisms of action including anti-inflammatory and immunoprotective effects, and its depletion is associated with intestinal injury. We previously showed that butyrate protects gut-liver injury during ethanol exposure. While the intestine is the largest immune organ in the body, little is known regarding the effects of ethanol on intestinal immune function. This work is aimed at investigating the effects of butyrate supplementation, in the form of the structured triglyceride tributyrin, on intestinal innate immune responses and oxidative stress following chronic-binge ethanol exposure in mice. Our work suggests that tributyrin supplementation preserved immune responses and reduced oxidative stress in the proximal colon during chronic-binge ethanol exposure. Our results also indicate a possible involvement of tributyrin in maintaining the integrity of intestinal villi vasculature disrupted by chronic-binge ethanol exposure.

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