Prophylactic antenatal N-Acetyl Cysteine administration combined with postnatal administration can decrease mortality and injury markers associated with necrotizing enterocolitis in a rat model.
Acetylcysteine
/ administration & dosage
Animals
Anti-Inflammatory Agents
/ administration & dosage
Caspase 3
/ metabolism
Enterocolitis, Necrotizing
/ drug therapy
Female
Free Radical Scavengers
/ administration & dosage
Interleukins
/ metabolism
Male
NF-kappa B
/ metabolism
Nitric Oxide Synthase Type II
/ metabolism
Rats
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha
/ metabolism
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
01
12
2019
accepted:
08
05
2020
entrez:
2
6
2020
pubmed:
2
6
2020
medline:
20
8
2020
Statut:
epublish
Résumé
Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of neonates, especially premature neonates. To date, there is no prophylactic treatment against NEC, except breast milk and slow increase in enteral feeding, and there is no antenatal prophylaxis. To assess possible protective effects of antenatal N-Acetyl Cysteine (NAC) against the intestinal pathophysiological changes associated with NEC in a rat model of NEC and against its associated mortality. Newborn Sprague-Dawley rats were divided into 5 groups: control (n = 33); NEC (n = 32)-subjected to hypoxia and formula feeding for 4 days to induce NEC; NEC-NAC (n = 34)-with induced NEC and concomitant postnatal NAC administration; NAC-NEC (n = 33)-born to dams treated with NAC for the last 3 days of pregnancy starting at gestational age of 18 days, and then subjected to induced NEC after birth; NAC-NEC-NAC (n = 36)-subjected to induced NEC with both prenatal and postnatal NAC treatment. At day of life 5, weight and survival of pups in the different groups were examined, and pups were euthanized. Ileal TNF-α, IL-6, IL-1β, IL-10, NFkB p65, iNOS and cleaved caspase 3 protein levels (western blot) and mRNA expression (RT-PCR) were compared between groups. Pup mortality was significantly reduced in the NAC-NEC-NAC group compared to NEC (11% vs. 34%, P<0.05). Ileal protein levels and mRNA expression of all injury markers tested except IL-10 were significantly increased in NEC compared to control. These markers were significantly reduced in all NAC treatment groups (NEC-NAC, NAC-NEC, and NAC-NEC-NAC) compared to NEC. The most pronounced decrease was observed in the NAC-NEC NAC group. Antenatal NAC decreases injury markers and mortality associated with NEC in a rat model. Antenatal administration of NAC may present a novel approach for NEC prophylaxis in pregnancies with risk for preterm birth.
Sections du résumé
BACKGROUND
Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of neonates, especially premature neonates. To date, there is no prophylactic treatment against NEC, except breast milk and slow increase in enteral feeding, and there is no antenatal prophylaxis.
AIMS
To assess possible protective effects of antenatal N-Acetyl Cysteine (NAC) against the intestinal pathophysiological changes associated with NEC in a rat model of NEC and against its associated mortality.
METHODS
Newborn Sprague-Dawley rats were divided into 5 groups: control (n = 33); NEC (n = 32)-subjected to hypoxia and formula feeding for 4 days to induce NEC; NEC-NAC (n = 34)-with induced NEC and concomitant postnatal NAC administration; NAC-NEC (n = 33)-born to dams treated with NAC for the last 3 days of pregnancy starting at gestational age of 18 days, and then subjected to induced NEC after birth; NAC-NEC-NAC (n = 36)-subjected to induced NEC with both prenatal and postnatal NAC treatment. At day of life 5, weight and survival of pups in the different groups were examined, and pups were euthanized. Ileal TNF-α, IL-6, IL-1β, IL-10, NFkB p65, iNOS and cleaved caspase 3 protein levels (western blot) and mRNA expression (RT-PCR) were compared between groups.
RESULTS
Pup mortality was significantly reduced in the NAC-NEC-NAC group compared to NEC (11% vs. 34%, P<0.05). Ileal protein levels and mRNA expression of all injury markers tested except IL-10 were significantly increased in NEC compared to control. These markers were significantly reduced in all NAC treatment groups (NEC-NAC, NAC-NEC, and NAC-NEC-NAC) compared to NEC. The most pronounced decrease was observed in the NAC-NEC NAC group.
CONCLUSIONS
Antenatal NAC decreases injury markers and mortality associated with NEC in a rat model. Antenatal administration of NAC may present a novel approach for NEC prophylaxis in pregnancies with risk for preterm birth.
Identifiants
pubmed: 32479520
doi: 10.1371/journal.pone.0233612
pii: PONE-D-19-33252
pmc: PMC7263616
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Free Radical Scavengers
0
Interleukins
0
NF-kappa B
0
Tumor Necrosis Factor-alpha
0
Nitric Oxide Synthase Type II
EC 1.14.13.39
Caspase 3
EC 3.4.22.-
Acetylcysteine
WYQ7N0BPYC
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0233612Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Trends Pharmacol Sci. 2013 Mar;34(3):167-77
pubmed: 23369637
J Clin Endocrinol Metab. 2003 Apr;88(4):1723-9
pubmed: 12679464
Clin Perinatol. 2013 Mar;40(1):109-24
pubmed: 23415267
Clin Perinatol. 1994 Jun;21(2):335-46
pubmed: 8070230
J Pediatr Surg. 2012 Sep;47(9):1652-7
pubmed: 22974601
J Pediatr Surg. 2012 Mar;47(3):540-50
pubmed: 22424351
Nutrients. 2020 Feb 19;12(2):
pubmed: 32092925
J Pediatr. 2014 Oct;165(4):672-7.e2
pubmed: 25064164
J Pediatr Surg. 2019 Dec;54(12):2520-2523
pubmed: 31668399
Int J Surg. 2020 Apr;76:79-87
pubmed: 32109650
Pediatr Res. 2014 Jul;76(1):100-8
pubmed: 24732104
J Pediatr Gastroenterol Nutr. 2020 May;70(5):664-680
pubmed: 32332478
Obstet Gynecol. 1989 Aug;74(2):247-53
pubmed: 2748061
J Surg Res. 2000 Jul;92(1):71-7
pubmed: 10864485
Am J Pathol. 2014 Oct;184(10):2768-78
pubmed: 25216938
Aging (Albany NY). 2019 Oct 14;11(19):8294-8312
pubmed: 31612867
J Matern Fetal Neonatal Med. 2012 Aug;25(8):1324-8
pubmed: 22046978
J Pediatr. 2014 May;164(5):980-5
pubmed: 24411521
J Nutr. 2000 Feb;130(2S Suppl):417S-419S
pubmed: 10721918
J Pediatr. 2016 Jan;168:67-76.e6
pubmed: 26545726
Am J Obstet Gynecol. 2009 Jun;200(6):665.e1-5
pubmed: 19344884
Exp Ther Med. 2018 Dec;16(6):5280-5285
pubmed: 30542485
J Pediatr Surg. 1997 Feb;32(2):275-82
pubmed: 9044137
Lancet. 1990 Dec 22-29;336(8730):1519-23
pubmed: 1979363
Oxid Med Cell Longev. 2018 Jul 2;2018:7397659
pubmed: 30057683
Pediatr Pathol. 1993 May-Jun;13(3):357-69
pubmed: 8516229
Pediatr Clin North Am. 1996 Apr;43(2):409-32
pubmed: 8614608
Crit Care Med. 2003 Nov;31(11):2574-8
pubmed: 14605526
Ann Surg. 2005 Jun;241(6):984-9; discussion 989-94
pubmed: 15912048
J Pediatr. 2020 May;220:86-92.e3
pubmed: 31982088
Surgery. 2004 Sep;136(3):557-66
pubmed: 15349102
Am J Obstet Gynecol. 2016 Oct;215(4):508.e1-6
pubmed: 27177525
Pediatr Res. 2004 Apr;55(4):622-9
pubmed: 14764921
J Pediatr. 1990 Jul;117(1 Pt 2):S47-51
pubmed: 2194011
Pediatr Clin North Am. 1979 May;26(2):327-44
pubmed: 379777
Am J Obstet Gynecol. 2003 Jan;188(1):203-8
pubmed: 12548218