The effects of pregnancy on ethanol clearance

Badger, Thomas M.; Hidestrand, Mats; Shankar, Kartik; McGuinn, W. David; Ronis, Martin J. J.

doi:10.1016/j.lfs.2005.02.019

Cited by 28 publications

(21 citation statements)

References 44 publications

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“…Previous studies have demonstrated that administering EtOH at doses as low as 1 g/kg to pregnant rat dams produces behavioral and physiological abnormalities in their offspring, including higher neonatal mortality and lower birth weights [48]. In our study, DHM reduced plasma [EtOH] to levels that might be achieved after administration of a lower (1.5-2 g/ kg) EtOH dose [70][71][72]. However, we also showed that birth and growth deficits were still evident in the offspring of the 1.5 g/kg EtOH alone group without DHM (Fig.…”

supporting

confidence: 49%

Dihydromyricetin Prevents Fetal Alcohol Exposure-Induced Behavioral and Physiological Deficits: The Roles of GABAA Receptors in Adolescence

et al. 2014

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Fetal alcohol exposure (FAE) can lead to a variety of behavioral and physiological disturbances later in life. Understanding how alcohol (ethanol, EtOH) affects fetal brain development is essential to guide the development of better therapeutics for FAE. One of EtOH's many pharmacological targets is the c-aminobutyric acid type A receptor (GABA A R), which plays a prominent role in early brain development. Acute EtOH potentiates inhibitory currents carried by certain GABA A R subtypes, whereas chronic EtOH leads to persistent alterations in GABA A R subunit composition, localization and function. We recently introduced a flavonoid compound, dihydromyricetin (DHM), which selectively antagonizes EtOH's intoxicating effects in vivo and in vitro at enhancing GABA A R function as a candidate for alcohol abuse pharmacotherapy. Here, we studied the effect of FAE on physiology, behavior and GABA A R function of early adolescent rats and tested the utility of DHM as a preventative treatment for FAE-induced disturbances. Gavage administration of EtOH (1.5, 2.5, or 5.0 g/kg) to rat dams on day 5, 8, 10, 12, and 15 of pregnancy dose-dependently reduced female/male offspring ratios (largely through decreased numbers of female offspring) and offspring body weights. FAE (2.5 g/kg) rats tested on postnatal days (P) 25-32 also exhibited increased anxiety and reduced pentylenetetrazol (PTZ)-induced seizure threshold. Patchclamp recordings from dentate gyrus granule cells (DGCs) in hippocampal slices from FAE (2.5 g/kg) rats at P25-35 revealed reduced sensitivity of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) and tonic current (I tonic ) to potentiation by zolpidem (0.3 lM). Interestingly, potentiation of mIPSCs by gaboxadol increased, while potentiation of I tonic decreased in DGCs from FAE rats. Coadministration of EtOH (1.5 or 2.5 g/kg) with DHM (1.0 mg/kg) in pregnant dams prevented all of the behavioral, physiological, and pharmacological alterations observed in FAE offspring. DHM administration alone in pregnant rats had no adverse effect on litter size, progeny weight, anxiety level, PTZ seizure threshold, or DGC GABA A R function. Our results indicate that FAE induces long-lasting alterations in physiology, behavior, and hippocampal GABA A R function and that these deficits are prevented by DHM co-treatment of EtOH-exposed dams. The absence of adverse side effects and the ability of DHM to prevent FAE consequences suggest that DHM is an attractive candidate for development as a treatment for prevention of fetal alcohol spectrum disorders.

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confidence: 49%

Dihydromyricetin Prevents Fetal Alcohol Exposure-Induced Behavioral and Physiological Deficits: The Roles of GABAA Receptors in Adolescence

et al. 2014

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“…Animals were housed in an Association Assessment and Accreditation of Laboratory Animal Care approved animal facility. Pregnant and cycling rats were intragastrically cannulated and infused for 15 d with either control or EtOH-containing diets at a dose of 13 g/kg/d as described previously (30,35). In addition, in a second study designed to examine vitamin D3 homeostasis during the anabolic phase of bone rebuilding in dams after weaning, timeimpregnated rats were surgically cannulated on gestational d 12, and had ad libitum access to commercial rodent chow (Harlan Teklad 8640; Harlan Sprague Dawley Inc., Indianapolis, IN) and water until their offspring were weaned.…”

Section: Animals and Experimental Treatmentsmentioning

confidence: 99%

“…We have previously demonstrated that UECs mirror blood EtOH concentrations (BECs) as a result of EtOH equilibration with body water (11,35,38). These concentrations are readily attainable in human alcoholics (39).…”

Section: Etoh Intake Reduces Serum 125 (Oh)2 D3 and Expression Of Rementioning

confidence: 99%

Chronic Ethanol Consumption Leads to Disruption of Vitamin D3 Homeostasis Associated with Induction of Renal 1,25 Dihydroxyvitamin D3-24-Hydroxylase (CYP24A1)

et al. 2007

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Bone loss resulting from chronic ethanol (EtOH) abuse is frequently accompanied by altered vitamin D3 homeostasis. In the current study, we examined EtOH effects in a female rat model in which control or EtOH-containing diets were infused intragastrically. EtOH treatment reduced plasma 1,25-dihydroxycholecalciferol (1,25 (OH)2 D3) coincident with a decrease in renal CYP27B1 (25(OH)D3 1alpha-hydroxylase) mRNA and an increase in expression of renal CYP24A1 (1,25 (OH)2 D3- 24-hydroxylase). EtOH induction of CYP24A1 occurred as a result of increased transcription and was also observed in vitro in primary cultures of rat renal proximal tubule cells (RPTCs) and in NRK-52E cells. Synergistic induction of CYP24A1 by EtOH in combination with 1,25 (OH)2 D3 was observed. The major EtOH metabolizing enzymes, alcohol dehydrogenase-1 and CYP2E1, were induced by EtOH in RPTCs. Inhibition of EtOH metabolism by 4-methylpyrazole inhibited the induction of CYP24A1 mRNA. CYP24A1 mRNA induction in RPTCs was also inhibited by the protein synthesis inhibitor cycloheximide. CYP24A1 was also induced after hydrogen peroxide treatment, and EtOH treatment of RPTCs resulted in production of reactive oxygen species as measured by flow cytometry using the fluorescent probe dichlorofluorescin acetate. In addition, inhibition of MAPK signaling pathways with the MAPK kinase inhibitor U0126 or the p38 inhibitor SB203580 inhibited EtOH induction of CYP24A1. Our data suggest that EtOH reduces circulating 1,25 (OH)2 D3 concentrations as the result of CYP24A1 induction that is mediated via MAPK activation resulting from renal oxidative stress produced by local metabolism of EtOH via CYP2E1 and antidiuretic hormone-1.

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“…Maternal hepatic functional adjustments include alterations in drug, lipid, cholesterol, bile acid, and glucose metabolism (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Pregnancy-induced changes in liver function tests have been reported in humans, including alterations of serum albumin and bilirubin levels, aspartate transaminase and alanine transaminase activites, and triglyceride and cholesterol concentrations in the blood (25)(26)(27)(28)(29).…”

Section: Introductionmentioning

confidence: 99%

Maternal Hepatic Growth Response to Pregnancy in the Mouse

Dai¹,

Bustamante²,

Myronovych³

et al. 2011

The Endocrine Society's 93rd Annual Meeting &Amp; Expo, June 4–7, 2011 - Boston

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Pregnancy is characterized by physiological adjustments in the maternal compartment. In this investigation, the influence of pregnancy on maternal liver was examined in CD-1 mice. Dramatic changes were observed in the size of the maternal liver during pregnancy. Livers doubled in weight from the nonpregnant state to day 18 of pregnancy. The pregnancy-induced hepatomegaly was a physiological event of liver growth confirmed by DNA content increase and detection of hepatocyte hyperplasia and hypertrophy. Growth of the liver was initiated following implantation and peaked at parturition. The expression and/or activities of key genes known to regulate liver regeneration, a phenomenon of liver growth compensatory to liver mass loss, were investigated. The results showed that pregnancy-dependent liver growth was associated with IL-6, TNF1α, NFkB, c-Jun, and IL-1β, but independent of HGF, FGF1, TNFR1, CAR, and PXR. Furthermore, maternal liver growth was associated with the activation of hepatic STAT3, β-catenin, and EGFR, but pregnancy did not activate hepatic c-Met. The findings suggest that the molecular mechanisms regulating pregnancy-induced liver growth and injury-induced liver regeneration exhibit overlapping features but are not identical. In summary, the liver of the mouse adapts to the demands of pregnancy via a dramatic growth response driven by hepatocyte proliferation and size increase. Remarkably, our findings provide a novel mouse model to investigate the regulation of hepatocyte proliferation, cell size increase, and liver growth.

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The effects of pregnancy on ethanol clearance

Cited by 28 publications

References 44 publications

Dihydromyricetin Prevents Fetal Alcohol Exposure-Induced Behavioral and Physiological Deficits: The Roles of GABAA Receptors in Adolescence

Dihydromyricetin Prevents Fetal Alcohol Exposure-Induced Behavioral and Physiological Deficits: The Roles of GABAA Receptors in Adolescence

Chronic Ethanol Consumption Leads to Disruption of Vitamin D3 Homeostasis Associated with Induction of Renal 1,25 Dihydroxyvitamin D3-24-Hydroxylase (CYP24A1)

Maternal Hepatic Growth Response to Pregnancy in the Mouse

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