Effect of Maternal Vitamin-A Administration on Fetal Lung Vitamin-A Stores in the Perinatal Rat

Shenai, Jayant P.; Chytil, Frank

doi:10.1159/000243286

Cited by 20 publications

(10 citation statements)

References 18 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the experiments described above, liver RE was analyzed in parallel with lung RE. As expected from previous studies (26)(27)(28), liver RE concentration exceeded lung RE concentration by z20-fold. However, in contrast to the greater effect of VARA, compared with VA alone, on RE in the lungs, RE in the liver was increased equally by VARA and VA alone (Fig.…”

Section: Histologysupporting

confidence: 89%

“…However, to our knowledge, an oral supplement of VA combined with RA has not been studied previously. VA supplementation alone, given to pregnant rats on gestational day 19, had been shown to increase the RE concentration in the lungs and liver of their fetuses, newborns, and neonates (26)(27)(28). In our studies, VA alone, given directly orally to neonates, also significantly increased the concentration of RE in the lungs and liver (Figs.…”

Section: Discussionsupporting

confidence: 65%

“…In the VA-adequate state, lung RE, mainly as retinyl palmitate, increased between gestational day 14 and 18, then declined abruptly before birth and remained relatively low from day 2 to 21, whereas liver RE increased before birth and increased even higher in the postnatal period (27). The offspring of VA-supplemented mothers showed the same temporal pattern, but their lung and liver RE concentrations were 1.7-to 7.1-fold higher (28). However, in the absence of maternal VA supplementation, neonates have very low reserves of VA compared with healthy adults (1), as a result of the very limited transfer of VA across the placenta (29).…”

mentioning

confidence: 91%

See 2 more Smart Citations

Vitamin A combined with retinoic acid increases retinol uptake and lung retinyl ester formation in a synergistic manner in neonatal rats

Ross

Ambalavanan

Zolfaghari

et al. 2006

Journal of Lipid Research

View full text Add to dashboard Cite

Vitamin A (VA) is stored in tissues predominantly as retinyl esters (REs), which provide substrate for the production of bioactive retinoids. Retinoic acid (RA), a principal metabolite, has been shown to induce postnatal lung development. To better understand lung RE storage, we compared VA (given as retinyl palmitate), RA, and a nutrient-metabolite combination, VARA, given orally on postnatal days 5-7, for their ability to increase lung RE in neonatal rats. VARA increased lung RE significantly [z14, 2.4, 2.1, and ,1 nmol/g for VARA, VA, RA, and control (C), respectively; P , 0.001]; the increase by VARA was more than additive compared with the effects of VA and RA alone. Lung histology and morphometry were unchanged. In a 6 h metabolic study, providing [ In conclusion, VARA, a 10:1 nutrientmetabolite combination, increased lung RE significantly compared with VA alone and could be a promising therapeutic option for enhancing the delivery of VA to the lungs.-Ross, A. C., N. Ambalavanan, R. Zolfaghari, and N-q. Li. Vitamin A combined with retinoic acid increases retinol uptake and lung retinyl ester formation in a synergistic manner in neonatal rats. Retinyl esters (REs) are the most abundant form of vitamin A (VA) in most tissues (1). The hydrolysis of RE generates retinol, which, through oxidative metabolism, yields retinoic acid (RA) (2), a retinoid hormone capable of activating nuclear retinoid receptors and thereby inducing or repressing the transcription of many genes (3-5). Among its many physiological actions, RA regulates cell proliferation, differentiation, and cell-cell interactions (6). For the lungs, retinoids are essential for normal morphogenesis in the fetal period, for maturation and remodeling in the perinatal and postnatal periods, and for maintenance of the fully matured lungs (7-10). In humans, the lungs undergo septation of the thick-walled air saccules in the perinatal period, beginning at approximately week 28 of gestation, with a 2-to 4-fold increase in the gas exchange surface area by weeks 30-40 (7, 11, 12). In rats and mice, septation and the formation of pulmonary alveoli occur mainly in the first 2 weeks of postnatal life (7,10,(12)(13)(14). Whereas a deficiency of dietary VA for 6 weeks resulted in an increased size of rat lung airspaces and reduced elastin in the parenchyma (15), the administration of RA to neonatal rats from postnatal day 3 to 14 increased the septation of the lungs (16,17). RA also attenuated the oxygen-induced inhibition of alveolarization in rats reared during the period of septation in a hyperoxic environment (18). Retinol has shown promise in reducing pulmonary dysfunction in a lamb model of preterm lung injury (19) and in clinical studies of preterm human infants susceptible to bronchopulmonary dysplasia (20)(21)(22)(23)(24)(25).The neonatal rodent is a useful model in which to study the biochemical and morphological development of the lungs in the perinatal period. Previous studies have characterized the ontogeny of RE storage in the lungs and liver...

show abstract

Section: Histologysupporting

confidence: 89%

Section: Discussionsupporting

confidence: 65%

mentioning

confidence: 91%

See 1 more Smart Citation

Vitamin A combined with retinoic acid increases retinol uptake and lung retinyl ester formation in a synergistic manner in neonatal rats

Ross

Ambalavanan

Zolfaghari

et al. 2006

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…In the rat, the concentration of RE in the lungs peaks around gestational day 18 (E18), then decreases progressively until the third postnatal day (P3) [27] . Although lung and liver REs were higher in the offspring of mothers supplemented with vitamin A during late pregnancy, the concentration of REs in the lungs still declined after birth [28] .…”

Section: Introductionmentioning

confidence: 89%

Retinoic Acid Combined with Vitamin A Synergizes to Increase Retinyl Ester Storage in the Lungs of Newborn and Dexamethasone-Treated Neonatal Rats

Ross¹,

Ambalavanan²

2007

Neonatology

View full text Add to dashboard Cite

Background: Retinyl esters (REs), the major storage form of vitamin A (retinol), provide substrates for the production of bioactive retinoids, including retinoic acid (RA), which are known to promote lung development and maturation. We previously showed that the nutrient-metabolite combination VARA (molar ratio 10 vitamin A to 1 RA), synergistically increased REs in the lungs of 1-week-old rats, compared to vitamin A or RA alone. Objectives: To test the hypotheses, first, that VARA is more effective in increasing lung RE than is vitamin A in newborn rats prior to alveolarization, and, second, that the effect of VARA is maintained during concurrent treatment with the glucocorticoid, dexamethasone (Dex). Methods: Newborn rats were treated with VARA, vitamin A alone, or oil (C) on postnatal days (P) 1–3, and RE in the lungs was quantified on P4, and again on P8 to assess retention. Additionally, neonatal rats were treated on P5–7 with VARA with and without Dex, and the lung and liver REs were quantified on P8. Results and Conclusions: Lung RE was nearly 8-fold higher in VARA compared to vitamin A-treated rats on P4 (p < 0.01) and 2.5-fold higher on P8. In neonates co-treated with Dex and VARA on P5–7, the elevation in lung RE on P8 by VARA was not antagonized by Dex, although Dex reduced growth. Lung morphology and development were not significantly altered. The VARA combination may significantly increase lung RE content even during concurrent Dex therapy. Because lung retinoids are important for lung maturation and repair, increasing lung RE may possibly have clinical benefit.

show abstract

“…In the rat, signifi cant storage of VA in the lungs starts in late gestation just before the onset of alveolization and surfactant synthesis ( 39 ). These stores are rapidly depleted during late pregnancy and postnatal life as the lungs are still developing ( 10,11,40 ). Weanling rats fed VA-defi cient diet showed the characteristics of keratinizing metaplasia in the trachea and the bronchopulmonary tree ( 36,41 ).…”

Section: The Expression Of Retinoid Homeostatic Genes Is Differentialmentioning

confidence: 99%

Acidic retinoids synergize with vitamin A to enhance retinol uptake and STRA6, LRAT, and CYP26B1 expression in neonatal lung

Ross

2010

Journal of Lipid Research

View full text Add to dashboard Cite

This article is available online at http://www.jlr.org but unlike VA, which is stored in tissues as retinyl ester (RE) and mobilized to produce RA ( 4 ), no signifi cant amount of RA is stored and the pool of RA turns over rapidly ( 5 ). RA and other retinoids have been shown to enhance alveolar septation in neonatal rats and mice (as reviewed in Refs. 2,3,6,7 ) and in some cases to improve lung repair after injury in adults ( 3,8,9 ). Most of the VA present in the lungs is in the form of RE ( 10-12 ). In fullterm infants, a process of signifi cant RE accumulation in the lungs has begun from the third trimester of fetal life, after which the stored RE becomes quickly depleted during late gestation and early postnatal life ( 10 ). By contrast, preterm infants often have low VA status at birth ( 13-15 ), which may contribute to poor lung maturation and increased susceptibility to respiratory diseases ( 16 ). Therefore, ways to improve RE storage in the lungs in the postnatal period could be useful clinically for supporting retinoid-requiring metabolic functions and aiding postnatal lung development.Previously, we tested a combination of VA (retinol) and RA, referred to as VARA (10:1 molar mixture of VA and RA) as an oral supplement for promoting lung RE formation ( 12 ). Lung RE increased synergistically, at least 4-fold more than for an equal amount of VA alone ( 17 ). As RA is not reduced to retinol in vivo and thus is not a substrate for tissue RE synthesis, the increase in RE in the lungs implies that RA plays a regulatory role in this organ, in some manner facilitating RE formation. The synergistic effect of VARA was selective for the lungs, as RE formation in the liver did not differ between VARA and an equal dose of VA only ( 12,17 ). In a metabolic study using [ 3 H]retinol to trace the uptake of newly absorbed retinol, we found that RA served to direct more of the [ 3 H]retinol tracer and, thus, the oral VA supplement, into the neonatal lung ( 12 ).Abstract Vitamin A (VA) is essential for fetal lung development and postnatal lung maturation. VA is stored mainly as retinyl esters (REs), which may be mobilized for production of retinoic acid (RA). This study was designed 1 ) to evaluate several acidic retinoids for their potential to increase RE in the lungs of VA-supplemented neonatal rats, and 2 ) to determine the expression of retinoid homeostatic genes related to retinol uptake, esterifi cation, and catabolism as possible mechanisms. When neonatal rats were treated with VA combined with any one of several acidic retinoids (RA, 9-cis -RA, or Am580, a stable analog of RA), lung RE increased ‫ف‬ 5-7 times more than after an equal amount of VA alone. Retinol uptake and esterifi cation during the period of absorption correlated with increased expression of both STRA6 (retinol-binding protein receptor) and LRAT (retinol esterifi cation), while a reduction in RE after 12 h in Am580-treated, VA-supplemented rats correlated with a strong and persistent increase in CYP26B1 (RA hydroxylase). We conclude that neona...

show abstract

Effect of Maternal Vitamin-A Administration on Fetal Lung Vitamin-A Stores in the Perinatal Rat

Cited by 20 publications

References 18 publications

Vitamin A combined with retinoic acid increases retinol uptake and lung retinyl ester formation in a synergistic manner in neonatal rats

Vitamin A combined with retinoic acid increases retinol uptake and lung retinyl ester formation in a synergistic manner in neonatal rats

Retinoic Acid Combined with Vitamin A Synergizes to Increase Retinyl Ester Storage in the Lungs of Newborn and Dexamethasone-Treated Neonatal Rats

Acidic retinoids synergize with vitamin A to enhance retinol uptake and STRA6, LRAT, and CYP26B1 expression in neonatal lung

Contact Info

Product

Resources

About