Placental transfer of rosiglitazone in the ex vivo human perfusion model

Holmes, Heather J.; Casey, Brian M.; Bawdon, Roger E.

doi:10.1016/j.ajog.2006.03.054

Cited by 25 publications

(9 citation statements)

References 18 publications

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“…However, animal studies (7) and limited human literature documenting that fetal exposure to RGZ during the first (10) and second (12) trimesters provide no evidence to suggest that RGZ is teratogenic. In line with the data presented here, transplacental transfer of RGZ has previously also been documented in an ex vivo human placental perfusion model (11).…”

Section: Discussionsupporting

confidence: 78%

Antenatally administered PPAR-γ agonist rosiglitazone prevents hyperoxia-induced neonatal rat lung injury

Rehan

Sakurai

Corral

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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The physiological development and homeostasis of the lung alveolus is determined by the expression of peroxisome proliferator-activated receptor-␥ (PPAR-␥) by the interstitial lipofibroblast. We have recently shown (Dasgupta C et al., Am J Physiol Lung Cell Mol Physiol 296: L1031-L1041, 2009.) that PPAR-␥ agonists administered postnatally accelerate lung maturation and prevent hyperoxia-induced lung injury. However, whether the same occurs antenatally is not known. The objective of this study was to test the hypothesis that the potent PPAR-␥ agonist rosiglitazone (RGZ), administered antenatally, enhances fetal lung maturation and protects against hyperoxia-induced neonatal lung injury. Sprague-Dawley rat dams were administered either diluent or RGZ (3 mg/kg), at late gestation, to determine its effect on lung maturation and on hyperoxia (95% O 2 exposure for 24 h)-induced neonatal lung injury. The lungs were examined for the expression of specific markers of alveolar development (surfactant proteins A and B, cholinephosphate cytidylyltransferase-␣, leptin receptor, triglyceride uptake, and [ 3 H]choline incorporation into saturated phosphatidylcholine) and injury/repair, in particular, the markers of transforming growth factor-␤ signaling (activin receptor-like kinase-5, SMAD3, lymphoid enhancer factor-1, fibronectin, and calponin). Overall, antenatal RGZ accelerated lung maturation and blocked the inhibition of alveolar sacculation and septal wall thinning by hyperoxia. RGZ specifically stimulated the development of the alveolar epithelial type II cell, the lipofibroblast, and the vasculature. The increased expression of the transforming growth factor-␤ intermediates, such as SMAD3 and lymphoid enhancer factor-1, implicated in hyperoxic lung injury, was also blocked by antenatal RGZ treatment. In conclusion, PPAR-␥ agonists can enhance fetal lung maturation and can effectively prevent hyperoxia-induced neonatal lung injury. lung development; peroxisome proliferator-activated receptor-␥; surfactant; lipofibroblast; hyperoxia SEVERAL LINES OF EVIDENCE suggest that lipids are cytoprotective against oxygen free radical lung injury in vitro and in vivo (5,23,37). Investigators have suggested that the greater oxygen tolerance of newborn rats and mice, compared with their adult counterparts, relates, in part, to the greater amount of triglyceride in the lipid fraction of the newborn compared with the adult lung (14,24,25,37). Feeding pregnant rats a high triglyceride diet results in increased triglyceride content in the lungs of their offspring, increased survival, and improved pathological status after prolonged hyperoxic exposure (25). In contrast, newborn offspring of rats fed low-polyunsaturated fatty acid diets are more susceptible to pulmonary oxygen toxicity and early lethality in hyperoxia (24). Furthermore, Kehrer and Autor (14) demonstrated that increasing the saturated fatty acid composition of lung triglycerides in adult rats by dietary manipulation produced increased susceptibility to oxygen toxicity.Ou...

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Section: Discussionsupporting

confidence: 78%

Antenatally administered PPAR-γ agonist rosiglitazone prevents hyperoxia-induced neonatal rat lung injury

Rehan

Sakurai

Corral

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…The transplacental transfer of rosiglitazone has already been shown in an ex vivo human perfusion model [15] as well as in an in vivo study performed in rats (3 mg/kg/day) [6]. At 24 h after birth, we observed an increase in the expression of PPARγ - a factor which is known to be induced in fetal lungs by rosiglitazone -, which suggests materno-fetal transfer.…”

Section: Discussionsupporting

confidence: 54%

Transplacental Administration of Rosiglitazone Attenuates Hyperoxic Lung Injury in a Preterm Rabbit Model

Richter

Toelen²,

Nagatomo³

et al. 2015

Fetal Diagn Ther

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Introduction: Continuous improvements in perinatal care have allowed the survival of increasingly more prematurely born infants. The establishment of respiration in an extremely immature yet still developing lung results in chronic lung injury with significant mortality and morbidity. We experimentally evaluated a novel medical strategy to prevent hyperoxia-induced lung injury by prenatal rosiglitazone. Materials and Methods: Pregnant rabbits were injected with saline or rosiglitazone (3 mg/kg) 48 and 24 h prior to preterm delivery at 28 days of gestation (term = 31 days). The pups were held in normoxia (21% O₂) or hyperoxia (>95% O₂), and assessment was done at three different time points (1 h, 24 h and 7 days). Results: The administration of rosiglitazone resulted in a significant decrease in tissue damping (resistance) on day 7. Furthermore, significantly increased expression of vascular endothelial growth factor, fetal liver kinase 1 and surfactant protein B immediately after delivery was noted by immunohistochemistery. On day 7, there was a more mature lung parenchymal architecture in rosiglitazone-exposed pups. Discussion: In a preterm rabbit model, prenatal maternal administration of rosiglitazone attenuates neonatal hyperoxic lung injury and results in a more mature pulmonary parenchyma.

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“…Rosiglitazone had no untoward effects on the growth and morphology of an in vitro rat embryo culture model despite concentrations as high as 10 times human peak plasma levels (58). Studies on early human pregnancy have shown that rosiglitazone can be transported across the placenta in the late phase of the first trimester from 8-to-12 weeks (59) but in an ex vivo human perfusion model there was negligible transfer of rosiglitazone across the placenta (60). This would suggest that it may be safe to take the TZD up until the time a pregnancy is confirmed.…”

Section: Discussionmentioning

confidence: 99%

PPAR-gamma receptor ligand induces regression of endometrial explants in baboons: A prospective, randomized, placebo- and drug-controlled study

Lebovic

Mwenda

Chai

et al. 2007

Fertility and Sterility

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Objective-To determine the effects of a thiazolidinedione (TZD) agonist of peroxisome proliferator-activated receptor (PPAR)-γ, rosiglitazone, in a baboon model of established endometriosis.Design-Prospective, randomized, placebo-controlled study.Setting-Experimental surgery laboratory at the Institute of Primate Research in Nairobi, Kenya.Animal(s)-Endometriosis was induced using intrapelvic injection of eutopic menstrual endometrium in 12 female baboons with a normal pelvis that had undergone at least one menstrual cycle since the time of captivity.Intervention(s)-Induction of endometriosis by laparoscopy was performed in 12 baboons with a normal pelvis. Endometrial tissue was extracted from each baboon by curettage and a standard amount of endometrium was then seeded onto several peritoneal sites as previously described. About 34-68 days after the induction of laparoscopy, a pre-treatment laparoscopy (baseline disease assessment) was performed in the baboons to record the extent of endometriotic lesions. The 12 baboons were randomized into 3 groups and treated from the day after the staging laparoscopy for a total duration of 30 days. They received either PBS tablets (n=4, placebo control; placebo tablets once a day by mouth for 30 days), GnRH-antagonists (n=4, active control; Ganirelix acetate 125 μg/day for 30 days) or rosiglitazone (n=4, test drug, 2 mg by mouth each day for 30 days). A 3 rd and final laparoscopy on day 30 after the start of treatment was performed to record the extent of endometriosis. The type of lesion (typical, red, white and suspicious) was recorded. Biopsies were obtained to confirm the histological presence of endometriosis.Main Outcome Measure(s)-A videolaparoscopy was performed 30 days after treatment to document the number and surface area of endometriotic lesions as well as to calculate the revised American Society for Reproductive Medicine score (rAFS) and stage.Corresponding author Dan I. Lebovic, M.D., M.A., Department of Obstetrics and Gynecology, University of Michigan, Tel: 734-615-8257, Fax: 734-647-1006, E-mail: lebovic@umich.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

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Placental transfer of rosiglitazone in the ex vivo human perfusion model

Cited by 25 publications

References 18 publications

Antenatally administered PPAR-γ agonist rosiglitazone prevents hyperoxia-induced neonatal rat lung injury

Antenatally administered PPAR-γ agonist rosiglitazone prevents hyperoxia-induced neonatal rat lung injury

Transplacental Administration of Rosiglitazone Attenuates Hyperoxic Lung Injury in a Preterm Rabbit Model

PPAR-gamma receptor ligand induces regression of endometrial explants in baboons: A prospective, randomized, placebo- and drug-controlled study

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