Blood–Placental Barrier Transfers and Pharmacokinetics of Unbound Morphine in Pregnant Rats with Multiple Microdialysis Systems

Author(s):  
I-Hsin Lin ◽  
Ling Yang ◽  
Thomas Y. Hsueh ◽  
Tung-Hu Tsai
2014 ◽  
Vol 4 (6) ◽  
pp. 232
Author(s):  
Francis Law ◽  
Grace Poon ◽  
Y. C. Chui ◽  
Shao-Xiong He

Background: Many species of hallucinogenic mushrooms have been found in the genus Psilocybe. The main psychoactive chemicals of Psilocybe mushrooms are psilocin and its phosphoryloxy derivative, psilocybin. In addition to its psychedelic effects, psilocybin is an effective agent to lift the mood of depressed patients with terminal cancers.Objective: To study the dispositional kinetics of 14C-psilocin in pregnant rats after intravenous injection, to calculate tissue dose surrogates i.e., tissue 14C concentration and area under the concentration-time curve using the experimental data, to quantify trans-placental passage of psilocin and/or its metabolites, and to identify new psilocin metabolite(s) in rat urine.Methods: A group of 15 pregnant Wistar rats weighing between 0.30-0.36 kg was used in the study. Each rat was given a single dose of 7.5 mg/kg 14C-psilocini.v. Three rats were randomly selected and sacrificed at 0.5, 1.0, 2.0, 4.0, and 8.0 hr post-dosing. The maternal and fetal tissues were quickly removed and the radioactivity in these tissues determined by liquid scintillation counting.In a separate study, urine samples were collected from 6 male Wistar rats after administering 15 mg/kg of unlabeled psilocin i.p. The urine samples were collected and extracted by chloroform-methanol (9:1 v/v) and analyzed using a gas chromatograph/mass spectrometer.Results: 14C-Psilocin crossed the placental barrier of pregnant rats readily after i.v. administration; maternal tissue 14C concentrations were found to be much higher than those in fetal tissues. The areas under the curve for maternal tissues also were much higher than the fetal tissues. In general, maternal tissues could be divided into the fast eliminating organ group, which included the brain (elimination half-life <13 hr) and the slow eliminating organ group, which included all fetal tissues (elimination half-life >13 hr). A new psilocin metabolite tentatively identified as dihydroxyindoleacetic acid was found in the urine.Conclusion: Our study showed that psilocin readily crossed the placental and blood-brain barriers of pregnant rats. Because psilocin was eliminated slowly from the fetal tissues of rats, human consumption of magic mushrooms should be avoided during pregnancy. Key words: magic mushrooms, psilocin, placental barrier, pregnant rats


2018 ◽  
Vol 122 ◽  
pp. 11-20 ◽  
Author(s):  
Sébastien Cambier ◽  
Masatake Fujimura ◽  
Jean-Paul Bourdineaud

2019 ◽  
Vol 34 (3) ◽  
pp. 307-322 ◽  
Author(s):  
Vendula Čečmanová ◽  
Pavel Houdek ◽  
Karolína Šuchmanová ◽  
Martin Sládek ◽  
Alena Sumová

The adult circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is resilient to glucocorticoids (GCs). The fetal rodent SCN resembles that of the adult in its organization of GC-sensitive peripheral tissues. We tested the hypothesis that the fetal SCN clock is sensitive to changes in GC levels. Maternal GCs must pass through the placenta to reach the fetal SCN. We show that the maternal but not the fetal part of the placenta harbors the autonomous circadian clock, which is reset by dexamethasone (DEX) and rhythmically expresses Hsd11b2. The results suggest the presence of a mechanism for rhythmic GC passage through the placental barrier, which is adjusted according to actual GC levels. GC receptors are expressed rhythmically in the laser-dissected fetal SCN samples. We demonstrate that hypothalamic explants containing the SCN of the mPer2 Luc mouse prepared at embryonic day (E)15 spontaneously develop rhythmicity within several days of culture, with dynamics varying among fetuses from the same litter. Culturing these explants in media enriched with DEX accelerates the development. At E17, treatment of the explants with DEX induces phase advances and phase delays of the rhythms depending on the timing of treatments, and the shifts are completely blocked by the GC receptor antagonist, mifepristone. The DEX-induced phase-response curve differs from that induced by the vehicle. The fetal SCN is sensitive to GCs in vivo because DEX administration to pregnant rats acutely downregulates c-fos expression specifically in the laser-dissected fetal SCN. Our results provide evidence that the rodent fetal SCN clock may respond to changes in GC levels.


1989 ◽  
Vol 67 (1) ◽  
pp. 1-4 ◽  
Author(s):  
S. Mulay ◽  
D. R. Varma

Transplacental passage of 125I-labelled synthetic rat atrial natriuretic peptide (ANP) was investigated in 20-day pregnant rats under pentobarbitone anesthesia. Although significant quantities of radioactivity were detected in the fetal plasma after maternal injections and in the maternal plasma after fetal injections of 125I-labelled synthetic ANP, no fraction of the placentally transferred radioactivity was due to intact ANP. Despite a rapid maternal and fetal metabolism of ANP, both maternal and fetal plasma radioactivity remained relatively stable for at least 3 h and less than 10% of the injected radioactivity was excreted in the maternal urine during a 90-min period. It is concluded that ANP is not transported in either direction across the placenta in rats.Key words: atrial natriuretic peptide, placental barrier, urinary excretion, maternal metabolism, fetal metabolism.


2021 ◽  
Vol 42 (3) ◽  
pp. 191-199
Author(s):  
Hye Sun Kim ◽  
Hyung‐Do Choi ◽  
Jeong‐Ki Pack ◽  
Nam Kim ◽  
Young Hwan Ahn

2018 ◽  
Vol 115 (10) ◽  
pp. E2429-E2436 ◽  
Author(s):  
Stefan Markovic ◽  
Anne Fages ◽  
Tangi Roussel ◽  
Ron Hadas ◽  
Alexander Brandis ◽  
...  

Placental functions, including transport and metabolism, play essential roles in pregnancy. This study assesses such processes in vivo, from a hyperpolarized MRI perspective. Hyperpolarized urea, bicarbonate, and pyruvate were administered to near-term pregnant rats, and all metabolites displayed distinctive behaviors. Little evidence of placental barrier crossing was observed for bicarbonate, at least within the timescales allowed by 13C relaxation. By contrast, urea was observed to cross the placental barrier, with signatures visible from certain fetal organs including the liver. This was further evidenced by the slower decay times observed for urea in placentas vis-à-vis other maternal compartments and validated by mass spectrometric analyses. A clear placental localization, as well as concurrent generation of hyperpolarized lactate, could also be detected for [1-13C]pyruvate. These metabolites also exhibited longer lifetimes in the placentas than in maternal arteries, consistent with a metabolic activity occurring past the trophoblastic interface. When extended to a model involving the administration of a preeclampsia-causing chemical, hyperpolarized MR revealed changes in urea’s transport, as well as decreases in placental glycolysis vs. the naïve animals. These distinct behaviors highlight the potential of hyperpolarized MR for the early, minimally invasive detection of aberrant placental metabolism.


Author(s):  
R. A. Turner ◽  
A. E. Rodin ◽  
D. K. Roberts

There have been many reports which establish a relationship between the pineal and sexual structures, including gonadal hypertrophy after pinealectomy, and gonadal atrophy after injection of pineal homogenates or of melatonin. In order to further delineate this relationship the pineals from 5 groups of female rats were studied by electron microscopy:ControlsPregnant ratsAfter 4 weekly injections of 0.1 mg. estradiol benzoate.After 8 daily injections of 150 mcgm. melatonin (pineal hormone).After 8 daily injections of 3 mg. serotonin (melatonin precursor).No ultrastructural differences were evident between the control, and the pregnancy and melatonin groups. However, the estradiol injected animals exhibited a marked increase in the amount and size of rough endoplasmic reticulum within the pineal cells.


Planta Medica ◽  
2011 ◽  
Vol 77 (12) ◽  
Author(s):  
F Namjooyan ◽  
M Panahi ◽  
F Ahmadpour ◽  
A Darvish ◽  
M Azemi ◽  
...  

1953 ◽  
Vol 14 (2) ◽  
pp. 181-188 ◽  
Author(s):  
Bengt Engfeldt ◽  
Gösta T. Hultquist

1964 ◽  
Vol 45 (4_Suppl) ◽  
pp. S139-S153 ◽  
Author(s):  
K. Junkmann ◽  
F. Neumann

ABSTRACT Experiments are described dealing with the mechanism of action of 6-chloro-Δ6-1,2α-methylene-17α-hydroxyprogesterone-acetate with regard to its anti-masculine effect on male rat foetuses, when administered to pregnant rats. It was shown that a marked direct anti-androgenic effect due to a competitive action on androgen receptors within the target organs, is probably the explanation of the mechanism of action. It was further shown that an oestrogenic effect or an appreciable inhibition of the pituitary gland respectively, can be ruled out as causative factors in the mechanism of action.


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