Treatment of bowel in experimental gastroschisis with a nitric oxide donor

Gonçalves, Frances Lilian Lanhellas; Bueno, Márcia Pereira; Schmidt, Augusto Frederico; Figueira, Rebeca Lopes; Sbragia, Lourenço

doi:10.1016/j.ajog.2014.09.025

Cited by 15 publications

(9 citation statements)

References 31 publications

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“…Maternal therapy with dexamethasone in a GS rat model showed reversion of intrauterine growth restriction (IUGR), reduction of intestinal weight and mucosal thickness ( 3 , 5 ). Treatment with hydrogel associated to an NO donor covering the GS fetal bowel loops as well as low concentration release of NO in the amniotic fluid reduced morphological parameters and intestinal wall thickness ( 4 , 27 ).…”

Section: Discussionmentioning

confidence: 99%

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Maternal administration of cannabidiol promotes an anti-inflammatory effect on the intestinal wall in a gastroschisis rat model

Callejas

Figueira

Gonçalves

et al. 2018

Braz J Med Biol Res

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Gastroschisis (GS) is an abdominal wall defect that results in histological and morphological changes leading to intestinal motility perturbation and impaired absorption of nutrients. Due to its anti-inflammatory, antioxidant, and neuroprotective effects, cannabidiol (CBD) has been used as a therapeutic agent in many diseases. Our aim was to test the effect of maternal CBD in the intestine of an experimental model of GS. Pregnant rats were treated over 3 days with CBD (30 mg/kg) after the surgical induction of GS (day 18.5 of gestation) and compared to controls. Fetuses were divided into 4 groups: 1) control (C); 2) C+CBD (CCBD); 3) gastroschisis (G), and 4) G+CBD (GCBD). On day 21.5 of gestation, the fetuses were harvested and evaluated for: a) body weight (BW), intestinal weight (IW), and IW/BW ratio; b) histometric analysis of the intestinal wall; c) immunohistochemically analysis of inflammation (iNOS) and nitrite/nitrate level. BW: GCBD was lower than CCBD (P<0.005), IW and IW/BW ratio: GCBD was smaller than G (P<0.005), GCBD presented lower thickness in all parameters compared to G (P<0.005), iNOS and nitrite/nitrate were lower concentration in GCBD than to G (P<0.005). Maternal use of CBD had a beneficial effect on the intestinal loops of GS with decreased nitrite/nitrate and iNOS expression.

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Section: Discussionmentioning

confidence: 99%

“…Molecular mechanisms involved in GS have not been completely unraveled. However, it is known that its inflammatory process causes histological and physiological changes associated with high local concentration of nitric oxide (NO) and nitric oxide synthases (NOS) ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Maternal administration of cannabidiol promotes an anti-inflammatory effect on the intestinal wall in a gastroschisis rat model

Callejas

Figueira

Gonçalves

et al. 2018

Braz J Med Biol Res

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“…95 In addition, they treated fetal GS with different concentrations of S-nitrosoglutathione (GNSO) a donor of NO and found that low concentration of GNSO could decrease the ID. 96 Régis et al investigated the contractility of the ileum in vitro and found an adaptive sensitivity to cholinergic response via an increase in the muscarinic receptor M 3 , with the frequency and the amplitude of rhythmic contractions reduced and increases in the contraction induced by electrical field stimulation. 97 Cavalcante et al studied the contractile profile of gastric fundus and antrum to better comprehension of the mechanism of fetal gastric dilation and found that the dilatation was not secondary to the bowel inflammation.…”

Section: Gastroschisis Model Surgically Created In Ratmentioning

confidence: 99%

Gastroschisis: State of the Art in Translating Experimental Research to the Bedside

et al. 2019

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The survival rate of newborns with gastroschisis (GS) has been increasing in the past decades; however, the morbidity continues to be high, mainly related to the length of hospitalization due to disturbances of motility, absorption, and risk of intestinal infections. The development of basic research with the creation of experimental models has provided enormous advances in the understanding of the pathophysiology of the disease. These models allowed the study of the target genes involved in the embryology of the defect, the influence of the amniotic fluid, and the use of drugs and fetal therapies in an attempt to reduce the intestinal damage and to provide a rapid return of intestinal motility. Our aim was to describe the main GS models and the translational, historical impact of these research advances on the disease.

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“…An actual therapeutic intervention directly aimed at improving the intestinal damage and function is yet to be widely adopted. To date, either clinically or mostly only experimentally, a number of prenatal strategies have been proposed, such as amnioexchange, amniotic fluid dilution, prenatal steroid administration, induced fetal diuresis, nitric oxide donors, and even intra-uterine repair of the defect, all with quite modest results and some risks (64)(65)(66)(67)(68).…”

Section: Trascet For Abdominal Wall Defectsmentioning

confidence: 99%

Transamniotic stem cell therapy: a novel strategy for the prenatal management of congenital anomalies

Fauza

2017

Pediatr Res

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Transamniotic stem cell therapy, or TRASCET, is an emerging therapeutic concept for the management of congenital anomalies based on the augmentation of the biological role of select populations of stem cells that already occur in the amniotic fluid, for targeted therapeutic benefit. Amniotic fluid-derived mesenchymal stem cells (afMSCs) have a central role in the enhanced ability of the fetus to repair tissue damage. This germane recent finding constitutes the biological foundation for the use of afMSCs in TRASCET. It has been shown experimentally that simple intra-amniotic delivery of afMSCs in large numbers can either elicit the repair, or significantly mitigate the effects associated with major congenital anomalies by boosting the activity that these cells normally have. For example, TRASCET can induce partial or complete coverage of experimental spina bifida by promoting the local formation of host-derived skin, thus protecting the spinal cord from further damage. In another example, it can significantly alleviate the bowel damage associated with gastroschisis, one of the most common major abdominal wall defects. Other applications involving different congenital anomalies and/or other stem cells present in the amniotic fluid in diseased pregnancies are currently under investigation in this freshly evolving facet of fetal stem cell therapy.

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Treatment of bowel in experimental gastroschisis with a nitric oxide donor

Cited by 15 publications

References 31 publications

Maternal administration of cannabidiol promotes an anti-inflammatory effect on the intestinal wall in a gastroschisis rat model

Maternal administration of cannabidiol promotes an anti-inflammatory effect on the intestinal wall in a gastroschisis rat model

Gastroschisis: State of the Art in Translating Experimental Research to the Bedside

Transamniotic stem cell therapy: a novel strategy for the prenatal management of congenital anomalies

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