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Updated: May 16, 2026
A Neonatal BALB/c Mouse Model of Necrotizing Enterocolitis
Published on: November 30, 2021
CDP-choline reduces severity of intestinal injury in a neonatal rat model of necrotizing enterocolitis
Merih Cetinkaya1, Mehmet Cansev, Ferhat Cekmez
1Division of Neonatology, Department of Pediatrics, Gulhane Military Medical Academy, Ankara, Turkey. drmerih@yahoo.com
Insights
Cytidine 5'-diphosphocholine (CDP-choline) treatment significantly reduced intestinal injury, inflammation, and apoptosis in a neonatal rat model of necrotizing enterocolitis (NEC). This suggests CDP-choline is a promising therapeutic agent for preventing NEC and improving infant gut health.
Area of Science:
- Neonatal research
- Gastroenterology
- Cellular biology
Background:
- Cytidine 5 -diphosphocholine (CDP-choline) is vital for phosphatidylcholine synthesis and intestinal mucosal defense.
- Necrotizing enterocolitis (NEC) is a severe intestinal condition in neonates.
- CDP-choline's potential cytoprotective effects in NEC require investigation.
Purpose of the Study:
- To evaluate CDP-choline's efficacy in mitigating intestinal cell damage in a neonatal rat NEC model.
- To assess CDP-choline's impact on membrane phospholipid levels, inflammation, and apoptosis in NEC.
- To determine CDP-choline's therapeutic potential for preventing NEC.
Main Methods:
- Newborn rats were divided into control, NEC, and NEC + CDP-choline groups.
- NEC was induced via formula feeding, hypoxia-hyperoxia, and cold stress.
- CDP-choline was administered intraperitoneally; apoptosis, cytokines, phospholipids, and enzyme activities were measured.
Main Results:
- CDP-choline treatment significantly improved clinical and histological NEC scores, reducing apoptosis and inflammation.
- CDP-choline preserved antioxidant enzyme activity and enhanced intestinal membrane phospholipid levels.
- Long-term follow-up showed increased body weight, reduced sickness, and improved survival in CDP-choline treated pups.
Conclusions:
- CDP-choline demonstrates significant beneficial effects on intestinal injury in a neonatal rat NEC model.
- The findings suggest CDP-choline as a potential therapeutic agent for preventing and treating NEC.
Background:
Cytidine 5'-diphosphocholine (CDP-choline) is an endogenous intermediate in the biosynthesis of phosphatidylcholine, a contributor to the mucosal defense of the intestine. The aim of this study was to evaluate the possible cytoprotective effect of CDP-choline treatment on intestinal cell damage, membrane phospholipid content, inflammation, and apoptosis in a neonatal rat model of necrotizing enterocolitis (NEC).
Methods:
We divided a total of 30 newborn pups into three groups: control, NEC, and NEC + CDP-choline. We induced NEC by enteral formula feeding, exposure to hypoxia-hyperoxia, and cold stress. We administered CDP-choline intraperitoneally at 300 mg/kg/d for 3 d starting from the first day of life. We evaluated apoptosis macroscopically and histopathologically in combination with proinflammatory cytokines in the gut samples. Moreover, we determined membrane phospholipid levels as well as activities of xanthine oxidase, superoxide dismutase, glutathione peroxidase, and myeloperoxidase enzymes and the malondialdehyde content of intestinal tissue.
Results:
Mean clinical sickness score, macroscopic gut assessment score, and intestinal injury score were significantly improved, whereas mean apoptosis score and caspase-3 levels were significantly reduced in pups in the NEC + CDP-choline group compared with the NEC group. Tissue proinflammatory cytokine (interleukin-1β, interleukin-6, and tumor necrosis factor-α) levels as well as tissue malondialdehyde content and myeloperoxidase activities were reduced, whereas glutathione peroxidase and superoxide dismutase activities were preserved in the NEC + CDP-choline group. In addition, NEC damage reduced intestinal tissue membrane phospholipids, whereas CDP-choline significantly enhanced total phospholipid and phosphatidylcholine levels. Long-term follow-up in additional experiments revealed increased body weight, decreased clinical sickness scores, and enhanced survival in CDP-choline-receiving versus saline-receiving pups with NEC lesions.
Conclusions:
Our study reports, for the first time, beneficial effects of CDP-choline treatment on intestinal injury in a neonatal rat model of NEC. Our data suggest that CDP-choline may be used as an effective therapeutic agent to prevent NEC.
