The developing central nervous system is a primary target of ethanol toxicity. The teratogenic effect of ethanol may result from its action on prostaglandins. Prostaglandins are generated through the release of arachidonic acid (AA) by the action of cytosolic phospholipase A2 (cPLA2) on membrane-bound phospholipids and the catalytic conversion of AA to prostaglandin E2 (PGE2) by cyclo-oxygenase (COX). COX is expressed in two isoforms, constitutive COX1 and inducible COX2. Cultured astrocytes and neurons from immature cerebral cortex were used as in vitro models to investigate the effect of ethanol on PGE2 synthesis. In both cell types, neither the activity nor the expression of cPLA2 was affected by ethanol. PGE2 was synthesized by astrocytes and neurons. Ethanol (200–400 mg/dL for 24 h) significantly increased PGE2 production in both cell types and the ethanol-induced increase in PGE2 accumulation in astrocytes was significantly greater than in neurons. These increases resulted from the effects of ethanol on COX. Overall COX activity was up-regulated by ethanol in astrocytes and neurons, and indomethacin, a nonselective blocker for COX, eliminated the ethanol-induced increases of COX activity in both cell types. Increased COX activity in astrocytes resulted from an increase in COX2 expression. NS-398, a selective COX2 blocker, completely inhibited ethanol-induced alterations in COX activity. In neurons, however, ethanol had a direct effect on COX activity in the absence of a change in COX expression. NS-398 only partially blocked ethanol-induced increases in neuronal COX activity. Thus, astrocytes are a primary target of ethanol and ethanol-induced increases in glial PGE2 synthesis are mediated by COX, principally COX2. Ethanol toxicity may be mediated through PGE2 in immature cortical cells.

Differential effects of ethanol on the expression of cyclo-oxygenase in cultured cortical astrocytes and neurons.

Background: The mechanisms by which maternal ethanol abuse during pregnancy causes neurodevelopmental injury in the fetus are not well understood The purpose of this study was to use a chronically instrumented fetal sheep model system to determine if a binge pattern of ethanol exposure administered throughout the third trimester reduced fetal arterial partial pressure of oxygen (P a O 2 ); a positive finding would support the hypothesis that fetal hypoxemia may play a role in mediating ethanol-related birth defects Methods: Pregnant ewes received saline or 075, 125, 15, or 175 g/kg of ethanol intravenously over 1 hr beginning on day 109 of gestation (term = 145 days) for 3 consecutive days per week followed by 4 days without exposure The fetuses were surgically instrumented on day 113, and experiments were performed on days 118 or 132, the 6th and the 12th ethanol exposure, respectively Results: Ethanol infusions resulted in peak blood ethanol concentrations of 808 ± 65, 1825 ± 135, 2244 ± 139, and 2606 ± 200 mg/dl ± SEM (maternal) and 700 ± 59, 1497 ± 90, 2169 ± 140, and 2333 ± 198 mg/dl ± SEM (fetal) in response to the 075, 125, 15, and 175 g/kg doses, respectively Maternal and fetal heart rate and maternal blood pressure increased whereas fetal blood pressure decreased in a dose-dependent manner in response to ethanol infusions Maternal and fetal arterial pH decreased and arterial partial pressures of carbon dioxide increased in response to ethanol infusions Maternal P a O 2 decreased whereas fetal P a O 2 did not change in response to ethanol infusions Conclusions: A binge ethanol exposure paradigm, three consecutive days per week throughout the third trimester at ethanol doses that created blood ethanol concentrations commonly achieved by human ethanol abusers, resulted in changes in maternal and fetal heart rate, changes in blood pressure, hypercapnea, acidemia, and maternal, but not fetal, hypoxemia We conclude that in an ovine model system, ethanol doses that create blood ethanol concentrations as high as 260 mg/dl do not result in fetal hypoxemia Remaining issues to address with this model system are whether neurodevelopmental injuries that are associated with maternal ethanol abuse are mediated by a reduction in fetal cerebral blood flow, fetal hypercapnea, or acidemia

Third trimester binge ethanol exposure results in fetal hypercapnea and acidemia but not hypoxemia in pregnant sheep.

It is now known that chronic consumption of excessive amounts of alcohol is a major source of social and medical problems. Ethanol-mediated glial cell activation may lead to neuron damage in many ways, including the formation of free radicals and production of pro-inflammatory molecules. Vitamin C (vit-C) is an essential dietary nutrient required as a co-factor for many enzymes and a very efficient antioxidant, protecting cells against free radical-mediated damage. The objective of this study was to evaluate the protective effects of vit-C on glial cell activation and viability against ethanol-mediated toxicity. Human brain astrocyte cells (HA) were exposed to ethanol (0, 50, and 350 mmol/L) for 24 h. We found that glial cells incubated with different concentrations of vit-C increase their vit-C in a dose-dependent manner. HA incubated with 0, 50 or 350 mmol/L of ethanol for up to 24 h showed toxic effects that were proportional to the levels of ethanol in the medium, HA showed increased levels of heat shock protein (Hsp70). However, cells enriched with vit-C before being exposed to ethanol, were better protected against the alcohol-mediated toxicity than non-supplemented cells, and showed significantly lower concentrations of Hsp70. Ethanol also caused increased expression of cyclooxygenase-2 (COX-2) and synthesis of prostaglandin E2 (PGE2), which were reduced by vit-C. In summary, HA supplemented with vit-C were significantly more resistant to the ethanol-mediated toxic effects.

Protective effect of vitamin C against the ethanol mediated toxic effects on human brain glial cells

Effect of ethanol on thromboxane and prostacyclin production in the human placenta.

The cerebral cortex is a target site of ethanol teratogenesis. L-Glutamate is a major excitatory neurotransmitter that plays an important neurotrophic role in brain development. It has been proposed that optimal function of the glutamate neuronal system is required for normal brain development; overactivation could lead to excitotoxic-induced neuronal injury, whereas underactivation could delay/restrict brain development. The objective of this study was to test the hypothesis that acute in vivo ethanol exposure alters basal glutamate release in the fetal cerebral cortex. The experimental approach involved measuring fetal cortical extracellular glutamate concentration using the technique of in vivo microdialysis. Near-term fetal sheep were chronically instrumented with a microdialysis probe placed in the parasagittal cortex. At 124 +/- 3 days of gestation, the effects of maternal intravenous infusion of 2 g or 4 g ethanol/kg maternal body weight or an equivalent volume of saline, given as four equally divided doses over 5 hr, on fetal cerebral cortical extracellular glutamate concentration were determined. None of the three treatment regimens produced fetal or maternal demise during the time course of the study. There was an ethanol dose-dependent increase, p = 0.005, in extracellular glutamate concentration in the fetal cerebral cortex. This increase was paroxysmal in nature and was not directly related to the fetal blood ethanol concentration. In view of the proposed role for glutamate in neuronal development, this apparent ethanol-induced increase in glutamate release may be important in the pathogenesis of ethanol teratogenesis involving the cerebral cortex.

Dose-dependent effects of acute in vivo ethanol exposure on extracellular glutamate concentration in the cerebral cortex of the near-term fetal sheep

Experiments were conducted in 14 pregnant sheep to determine the effect of a 1-h maternal infusion of ethanol (1 g/kg maternal body wt) on placental efflux of prostaglandin E2 (PGE2), umbilical blood flow (Qum), and carbohydrate metabolism at 123-130 days gestation. This ethanol dosage regimen produced peak ethanol concentrations in fetal and maternal blood in the range of 1.48-1.64 mg/ml at the end of the infusion. Umbilical venous and fetal arterial PGE2 concentrations increased (P < 0.05) from 315 +/- 47 and 202 +/- 25 pg/ml to 740 +/- 172 and 489 +/- 67 pg/ml, respectively, at the end of the infusion. Placental secretion of PGE2 into the fetal circulation increased by 45% (P < 0.05). Uterine venous and maternal arterial PGE2 concentration increased (P < 0.05) from 370 +/- 27 and 262 +/- 28 pg/ml to 705 +/- 51 and 487 +/- 69 pg/ml, respectively. Fetal and maternal blood glucose concentration decreased (P < 0.05) from 0.98 +/- 0.11 and 2.88 +/- 0.25 mmol/l to 0.81 +/- 0.21 and 2.44 +/- 0.16 mmol/l, respectively. Fetal and maternal blood lactate concentration increased (P < 0.05) from 1.40 +/- 0.11 and 0.68 +/- 0.07 mmol/l to 1.67 +/- 0.14 and 1.82 +/- 0.16 mmol/l, respectively. Qum, fetal heart rate, fetal blood pressure, and fetal and maternal blood gases were unchanged by the ethanol infusion. These results support the hypothesis that the placenta is the major source of the elevated fetal and maternal plasma PGE2 concentrations produced in pregnant sheep by maternal ethanol administration.

Increased uteroplacental production of prostaglandin-e2 during ethanol infusion

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

D. M. Olson

Author Tools

Chat about Author

Papers

Increased uteroplacental production of prostaglandin-e2 during ethanol infusion