Poly(ADP-ribose) polymerase-1: A novel therapeutic target in necrotizing enterocolitis

Peter J. Giannone, Alicia A. Alcamo, Brandon L. Schanbacher, Craig A. Nankervis, Gail E. Besner, John A. Bauer

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of infancy, afflicting 11% of infants born 22-28 wk GA. Both inflammation and oxidation may be involved in NEC pathogenesis through reactive nitrogen species production, protein oxidation, and DNA damage. Poly(ADP-ribose) polymerase-1 (PARP-1) is a critical enzyme activated to facilitate DNA repair using nicotinamide adenine dinucleotide (NAD +) as a substrate. However, in the presence of severe oxidative stress and DNA damage, PARP-1 overactivation may ensue, depleting cells of NAD + and ATP, killing them by metabolic catastrophe. Here, we tested the hypothesis that NO dysregulation in intestinal epithelial cells during NEC leads to marked PARP-1 expression and that administration of a PARP-1 inhibitor (nicotinamide) attenuates intestinal injury in a newborn rat model of NEC. In this model, 56% of control pups developed NEC (any stage) versus 14% of pups receiving nicotinamide. Forty-four percent of control pups developed high-grade NEC (grades 3-4), whereas only 7% of pups receiving nicotinamide developed high-grade NEC. Nicotinamide treatment protects pups against intestinal injury incurred in the newborn rat NEC model. We speculate that PARP-1 overactivation in NEC may drive mucosal cell death in this disease and that PARP-1 may be a novel therapeutic target in NEC.

Original languageEnglish
Pages (from-to)67-71
Number of pages5
JournalPediatric Research
Issue number1
StatePublished - Jul 2011

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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