Estrogen Alleviates Oxidative Bowel Injury and Neuroinflammation in Necrotizing Enterocolitis

Area of Science:

• Neonatal research
• Pharmacology
• Gastroenterology

Background:

• Necrotizing enterocolitis (NEC) is a severe condition in neonates with high mortality.
• Novel therapeutic strategies are crucial for improving NEC outcomes.
• Estrogen signaling's role in NEC is under investigation.

Purpose of the Study:

• To investigate the therapeutic potential of estrogen receptor agonists in mitigating NEC-induced intestinal and brain injury.
• To evaluate the effects of specific estrogen receptor alpha (ERα) and ERβ agonists on NEC models.

Main Methods:

• A rat model of NEC was established using Sprague-Dawley pups subjected to maternal separation, formula feeding, and hypoxia.
• NEC-induced pups were treated with vehicle, ERα agonist (propyl pyrazole triol), ERβ agonist (diarylpropionitrile), or 17β-estradiol.
• Intestinal and brain tissues were collected for histological, biochemical, and gene expression analysis.

Main Results:

• NEC induced significant proinflammatory cytokine elevation, apoptosis, and oxidative injury in both intestinal and brain tissues.
• Treatment with 17β-estradiol or ER agonists reduced oxidative injury, upregulated neurotrophic factors (nerve growth factor, brain-derived neurotrophic factor), and normalized ER gene expression.
• Estrogen agonists improved survival rates and clinical conditions in NEC-affected pups, and normalized claudin-3 expression.

Conclusions:

• Activation of estrogen signaling pathways through receptor agonists effectively alleviated NEC-induced intestinal and cerebral damage.
• Estrogen agonists represent promising candidates for the prevention and treatment of necrotizing enterocolitis in neonates.