Poly(ADP-ribose) polymerase-1: a novel therapeutic target in necrotizing enterocolitis
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Updated: Jun 3, 2026
A Novel Human Epithelial Enteroid Model of Necrotizing Enterocolitis
Published on: April 10, 2019
Peter J Giannone1, Alicia A Alcamo, Brandon L Schanbacher
1Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43205, USA. peter.giannone@nationwidechildrens.org
Insights
Necrotizing enterocolitis (NEC) involves inflammation and oxidation. A PARP-1 inhibitor, nicotinamide, significantly reduced NEC severity and injury in a newborn rat model, suggesting PARP-1 as a therapeutic target.
Area of Science:
- Neonatal Medicine
- Gastroenterology
- Molecular Biology
Background:
- Necrotizing enterocolitis (NEC) is a common, severe gastrointestinal disease in premature infants.
- Oxidative stress and inflammation contribute to NEC pathogenesis, potentially involving reactive nitrogen species and DNA damage.
- Poly(ADP-ribose) polymerase-1 (PARP-1) is crucial for DNA repair but can cause cell death via NAD+ depletion when overactivated by severe damage.
Purpose of the Study:
- To investigate the role of nitric oxide (NO) dysregulation and PARP-1 overactivation in intestinal epithelial cells during NEC.
- To evaluate the therapeutic potential of a PARP-1 inhibitor, nicotinamide, in an experimental NEC model.
Main Methods:
- A newborn rat model was used to induce NEC.
- Rats were treated with nicotinamide, a PARP-1 inhibitor.
- Intestinal injury and NEC development were assessed in control and treated groups.
Main Results:
- 56% of control pups developed NEC, compared to only 14% of pups treated with nicotinamide.
- High-grade NEC (grades 3-4) occurred in 44% of controls versus 7% of nicotinamide-treated pups.
- Nicotinamide administration significantly protected pups against intestinal injury in the NEC model.
Conclusions:
- PARP-1 overactivation may contribute to mucosal cell death in NEC.
- Nicotinamide treatment demonstrates a protective effect against intestinal injury in a rat model of NEC.
- PARP-1 inhibition represents a potential novel therapeutic strategy for managing NEC.
Abstract:
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.
