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Updated: Jun 15, 2026
A Neonatal BALB/c Mouse Model of Necrotizing Enterocolitis
Published on: November 30, 2021
Activated protein C reduces intestinal injury in an experimental model of necrotizing enterocolitis
Abdullah Kumral1, Didem C Yesilirmak, Kazim Tugyan
1Department of Pediatrics, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
Insights
Activated protein C (APC) treatment reduced intestinal injury and apoptosis in a rat model of necrotizing enterocolitis. This protective effect was linked to decreased inflammatory cytokines and nitric oxide levels.
Area of Science:
- Neonatal research
- Gastroenterology
- Biomedical science
Background:
- Necrotizing enterocolitis (NEC) is a severe intestinal disease affecting premature infants.
- Activated protein C (APC), known for anticoagulation, also exhibits cytoprotective, anti-inflammatory, and anti-apoptotic properties.
- Limited research exists on APC's efficacy in NEC animal models.
Purpose of the Study:
- To investigate the therapeutic potential of activated protein C (APC) in a rat model of hypoxia-reoxygenation-induced intestinal injury.
- To evaluate APC's effects on histopathological damage, nitric oxide levels, apoptosis, and cytokine expression in the context of NEC.
Main Methods:
- Twenty-one Wistar albino rat pups were divided into control, hypoxia-reoxygenation (H-R) with saline, and H-R with APC treatment groups.
- Hypoxia was induced using carbon dioxide, followed by reoxygenation with oxygen.
- Intestinal tissue was analyzed for histopathology, nitrite, apoptosis, and cytokine levels (IL-1beta, TNF-alpha, IL-6).
Main Results:
- APC treatment significantly reduced intestinal injury scores compared to the saline-treated H-R group (P = .002).
- APC administration lowered elevated nitric oxide levels in the intestine (P = .001).
- APC significantly decreased apoptotic cell death and reduced levels of pro-inflammatory cytokines (IL-1beta, TNF-alpha, IL-6).
Conclusions:
- Activated protein C (APC) effectively attenuates intestinal injury and apoptosis in a rat model mimicking NEC.
- APC's protective mechanisms involve the downregulation of inflammatory cytokines and nitric oxide production.
- APC demonstrates potential as a therapeutic agent for necrotizing enterocolitis.
Background:
Necrotizing enterocolitis is a devastating intestinal disease of premature infants. Although activated protein C (APC) is well defined as a physiologic anticoagulant, emerging data suggest that it also has cytoprotective, antiinflammatory, and antiapoptotic properties. There is no study on active protein C administration for necrotizing enterocolitis in animal models.
Methods:
Twenty-one Wistar albino rat pups were divided into 3 groups: group 1 = control; group 2 = hypoxia-reoxygenation and saline; group 3 = hypoxia-reoxygenation and APC (0.2 mg/kg per day) treatment. On the 15th day, hypoxia was induced by placing the pups in a 100% carbon dioxide chamber for 5 minutes. After the hypoxia period, the pups were reoxygenated for 10 minutes with 100% oxygen and returned to their mothers. All pups were killed 4 hours after the hypoxia-reoxygenation period was over. The abdomen was opened, and representative samples of injured areas were taken for histopathologic examination, nitrite levels, apoptosis, and cytokine levels.
Results:
On histopathologic examination, injury scores in group 2 animals were found to be significantly higher than in group 3 animals (P = .002). Significantly increased intestinal nitric oxide levels were found in group 2 rats compared with the rats of groups 1 and 3 (P = .001 and P = .001, respectively). The APC treatment was significantly reduced "apoptotic cell death" in the bowel, when compared with vehicle-treated group. The proinflammatory cytokine levels (interleukin [IL]-1beta, tumor necrosis factor [TNF]-alpha, and IL-6) were significantly increased in hypoxia group as compared with control group. The concentration of cytokines, IL-1beta, IL-6, and TNF-alpha was reduced in the APC treatment group.
Conclusion:
The APC treatment attenuates hypoxia-reoxygenation induced with intestinal injury and decreased apoptotic cell index in this animal model. The protective effect of APC is associated with its ability to reduce the expression of inflammatory cytokines and nitric oxide.
