Sildenafil attenuates intestinal injury in necrotizing enterocolitis independently of endothelial nitric oxide synthase

•Necrotizing enterocolitis is a devastating disease that afflicts premature infants and for which targeted treatment options are lacking.•Sildenafil improves clinical outcomes and protects the intestine when administered orally in a murine model of necrotizing enterocolitis. This protection is provi...

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Bibliographic Details
Published in:Journal of pediatric surgery 2022-12, Vol.57 (12), p.967-973
Main Authors: Hunter, Chelsea E., Hosfield, Brian D., Mesfin, Fikir M., Pecoraro, Anthony R., Liu, Jianyun, Shelley, W. Christopher, Manohar, Krishna, Markel, Troy A.
Format: Article
Language:English
Subjects:
Endothelial nitric oxide synthase
ENOS
NEC
Necrotizing enterocolitis
Sildenafil
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Summary:•Necrotizing enterocolitis is a devastating disease that afflicts premature infants and for which targeted treatment options are lacking.•Sildenafil improves clinical outcomes and protects the intestine when administered orally in a murine model of necrotizing enterocolitis. This protection is provided through eNOS dependent and eNOS independent mechanisms. Necrotizing enterocolitis (NEC) is a devastating disease that impacts the intestine of premature infants. Sildenafil has shown benefit in colitis and ischemia/reperfusion models but has not been adequately studied in NEC. Sildenafil's best studied mechanism involves augmenting nitric oxide induced vasodilation. We hypothesized that sildenafil would improve outcomes during experimental NEC in an eNOS dependent manner. NEC was induced in five-day old mouse pups with gavage formula feeds plus intermittent hypoxia and hypothermia. Using wild type (WT) mice, the route of sildenafil administration was studied in the following groups: (1) breastfed controls, (2) NEC + oral (PO) sildenafil, (3) NEC + PO vehicle, (4) NEC + intraperitoneal (IP) sildenafil, (5) NEC + IP vehicle. The eNOS KO groups studied included: (1) breastfed controls, (2) NEC + PO sildenafil, (3) NEC + PO vehicle. Data were tested for normality and compared using t-tests or Mann-Whitney with a p-value
ISSN:0022-3468
1531-5037
DOI:10.1016/j.jpedsurg.2022.06.001