Acetaldehyde Production and Transfer by the Perfused Human Placental Cotyledon

Karl, Peter I.; Gordon, Barbara H. J.; Lieber, Charles S.; Fisher, Stanley E.

doi:10.1126/science.3175652

Cited by 58 publications

(11 citation statements)

References 29 publications

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“…19 The alcohol oxidation rate of the placenta is estimated at 45.6 nmol h À1 g À1 of tissue, whereas the oxidation rate of the alcohol in the adult liver is increased over 3900 fold at 178 mmol h À1 per g of tissue. 20 Because of the reduced ethanol oxidation capacity of placental ADH, the placenta does not appear to have a significant role in the oxidative metabolism of ethanol. While the placenta contains FAEE synthase activity, 21 the limited role of FAEE synthase in the normal metabolism of ethanol suggests that the non-oxidative pathway does not make a significant contribution to the ability of the placenta to metabolize alcohol.…”

Section: Bac and Aer For Mother Fetus And Newborn L Burd Et Almentioning

confidence: 99%

Prenatal alcohol exposure, blood alcohol concentrations and alcohol elimination rates for the mother, fetus and newborn

2012

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Fetal alcohol spectrum disorders (FASDs) are a common cause of intellectual impairment and birth defects. More recently, prenatal alcohol exposure (PAE) has been found to be a risk factor for fetal mortality, stillbirth and infant and child mortality. This has led to increased concern about detection and management of PAE. One to 2 h after maternal ingestion, fetal blood alcohol concentrations (BACs) reach levels nearly equivalent to maternal levels. Ethanol elimination by the fetus is impaired because of reduced metabolic capacity. Fetal exposure time is prolonged owing to the reuptake of amniotic-fluid containing ethanol by the fetus. Alcohol elimination from the fetus relies on the mother's metabolic capacity. Metabolic capacity among pregnant women varies eightfold (from 0.0025 to 0.02 g dl À1 h À1 ), which may help explain how similar amounts of ethanol consumption during pregnancy results in widely varying phenotypic presentations of FASD. At birth physiological changes alter the neonate's metabolic capacity and it rapidly rises to a mean value of 83.5% of the mother's capacity. FASDs are highly recurrent and younger siblings have increased risk. Detection of prenatal alcohol use offers an important opportunity for office-based interventions to decrease exposure for the remainder of pregnancy and identification of women who need substance abuse treatment. Mothers of children with FAS have been found to drink faster, get drunk quicker and to have higher BACs. A modest increase in the prevalence of a polymorphism of alcohol dehydrogenase, which increases susceptibility to adverse outcomes from PAE has been reported. Lastly, detection of alcohol use and appropriate management would decrease risk from PAE for subsequent pregnancies.

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Section: Bac and Aer For Mother Fetus And Newborn L Burd Et Almentioning

confidence: 99%

Prenatal alcohol exposure, blood alcohol concentrations and alcohol elimination rates for the mother, fetus and newborn

2012

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“…Other phaseⅠmetabolizing enzymes such as aldehyde dehydrogenases (ALDHs) participate in the detoxification of endogenous and exogenous compounds, including ethanol. The presence of this activity in human placenta may be relevant in the toxicity of a number of substances and for the gestational consequences of alcohol consumption [140] .…”

Section: Metabolic Barriermentioning

confidence: 99%

Excretion of biliary compounds during intrauterine life

Macı́as¹,

Marin²,

Serrano³

2009

WJG

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In adults, the hepatobiliary system, together with the kidney, constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine, respectively. However, during intrauterine life the biliary route of excretion for cholephilic compounds, such as bile acids and biliary pigments, is very poor. Although very early in pregnancy the fetal liver produces bile acids, bilirubin and biliverdin, these compounds cannot be efficiently eliminated by the fetal hepatobiliary system, owing to the immaturity of the excretory machinery in the fetal liver. Therefore, the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the placenta. Owing to the presence of detoxifying enzymes and specific transport systems at different locations of the placental barrier, such as the endothelial cells of chorionic vessels and trophoblast cells, this organ plays an important role in the hepatobiliary-like function during intrauterine life. The relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the mother. This may result in oxidative stress and apoptosis, mainly in the placenta and fetal liver, which might affect normal fetal development and challenge the fate of the pregnancy. The present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem.

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“…CYP-mediated metabolism in the placenta is more restricted than hepatic metabolism, but still placental CYP enzymes are capable of metabolizing several drugs and foreign chemicals (Hakkola et al, 1998;Pasanen, 1999). In addition to the CYP enzymes, other phase 1 metabolizing enzymes, such as alcohol dehydrogenase, have also been detected in the placenta (Karl et al, 1988). Among phase 2 enzyme activities, glutathione transferase, epoxide hydrolase, N-acetyltransferase, sulfotransferases, and UDP-glucuronoyl transferase are expressed in human placental tissue (Karl et al, 1988).…”

Section: Discussionmentioning

confidence: 98%

“…In addition to the CYP enzymes, other phase 1 metabolizing enzymes, such as alcohol dehydrogenase, have also been detected in the placenta (Karl et al, 1988). Among phase 2 enzyme activities, glutathione transferase, epoxide hydrolase, N-acetyltransferase, sulfotransferases, and UDP-glucuronoyl transferase are expressed in human placental tissue (Karl et al, 1988). Even though the metabolic activity of phase 2 enzymes in the placenta is low, at least some of these compounds are capable of xenobiotic metabolism (Hakkola et al, 1998).…”

Section: Discussionmentioning

confidence: 98%

Relation between some environmental pollutants and recurrent spontaneous abortion

Saad

El-Sikaily

Elbadawi

et al. 2016

Arabian Journal of Chemistry

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Reproductive health is exquisitely sensitive to characteristics of an individual's environment including physical, biological, behavioral, cultural and socioeconomic factors. This study was launched to elucidate the effect of the exposure to chemical pollutants as aromatic amines viz. (benzidine, mono-acetyl benzidine, diacetyl benzidine, a,b-naphthylamine) as well as the biological pollutants e.g., human cytomegalovirus (HCMV) as risk factors for recurrent spontaneous abortion (RSA) through determination of MDA as a marker of oxidative stress and determination of some antioxidant markers. The results of the current study revealed that the aborter mothers were being exposed to environmental pollutants as aromatic amines which were manifested by the presence of benzidine, mono-acetyl-benzidine, di-acetyl-benzidine, a,b-naphthylamine in most of their urine samples, where the level of aromatic amines were more 13.6, 10, 15, and 4-folds than the control group, respectively. Also, the data suggest that in early pregnancy failure there is an increase in markers of oxidative stress and a probable decrease in maternal antioxidant defenses (22 nmol/ ml and 17 mg/l, 550 U/l, respectively). Generation of ROS in large quantities, in the first trimester placenta which has limited antioxidant defenses may cause DNA damage, oxidation of protein and lipid resulting in extensive cell death. Also, it was demonstrated that high elevation of HCMV inhibits cytotrophoblasts proliferation, migration invasion and matrix metalloproteins (MMP) expres-* Corresponding author.

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Acetaldehyde Production and Transfer by the Perfused Human Placental Cotyledon

Cited by 58 publications

References 29 publications

Prenatal alcohol exposure, blood alcohol concentrations and alcohol elimination rates for the mother, fetus and newborn

Prenatal alcohol exposure, blood alcohol concentrations and alcohol elimination rates for the mother, fetus and newborn

Excretion of biliary compounds during intrauterine life

Relation between some environmental pollutants and recurrent spontaneous abortion

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