Overfeeding Can Cause NEC-Like Enterocolitis in Premature Rat Pups

• Published in: Neonatology (Basel, Switzerland) Vol. 97; no. 3; pp. 218 - 224
• Main Authors: Okada, Kyo, Fujii, Tohru, Ohtsuka, Yoshikazu, Yamakawa, Yoko, Izumi, Hirohisa, Yamashiro, Yuichiro, Shimizu, Toshiaki
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2010
• Subjects: Animals; Animals, Newborn; Animals, Suckling; Disease Models, Animal; Enterocolitis - etiology; Enterocolitis - pathology; Enterocolitis, Necrotizing - etiology; Enterocolitis, Necrotizing - pathology; Female; Humans; I-kappa B Proteins - genetics; I-kappa B Proteins - metabolism; Infant, Newborn; Infant, Premature, Diseases - pathology; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; NF-KappaB Inhibitor alpha; Original Paper; Overnutrition - complications; Overnutrition - pathology; PPAR gamma - genetics; PPAR gamma - metabolism; Pregnancy; Rats; Rats, Sprague-Dawley; Overfeeding of milk; Inhibitor of nuclear factor-ĸB; Neonatal necrotizing enterocolitis; Nuclear factor-ĸB; Peroxisome proliferator-activated receptor-γ
• ISSN: 1661-7800; 1661-7819
• DOI: 10.1159/000253150

Background: Neonatal necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in premature infants. The mortality rate associated with NEC is quite high and in most reports ranges from 20 to 30%. Despite extensive studies, the pathogenesis of NEC remains poorly understood. Objectives: To investigate the mechanisms of NEC in terms of inflammatory signaling in the intestine. Methods: A new enterocolitis model was established and examined the expression of inflammatory and anti-inflammatory signals in the intestines of rat pups. The premature rat pups, delivered by abdominal incision on day 20 of gestation (day 21 is considered as full term), were divided into three groups, and they were given a single administration of 0.05, 0.1, and 0.15 ml of formula milk via an orogastric catheter. After 24 h, the development of enterocolitis was evaluated by the presence of hemorrhagic enterocolitis, and the expression of signaling molecules, inhibitor of nuclear factor-ĸB (IĸB)-α/β and peroxisome proliferator-activated receptor (PPAR)-γ mRNA was examined by reverse transcription-polymerase chain reaction from inflamed and non-inflamed intestinal samples. Results: The incidence of enterocolitis increased with the volume of milk, and 50% of rat pups showed enterocolitis with a volume of 0.15 ml of milk. Expression of IĸB-α/β and PPAR-γ mRNA increased in inflamed intestine. Conclusions: Increased expression of IĸB-α/β suggested that the inflammatory mediator nuclear factor-ĸB is deeply involved in the pathogenesis of enterocolitis that can be easily introduced by overfeeding of milk ingestion in premature rat pups which mimic those seen in NEC. Increased expression of PPAR-γ may possibly regulate further development of enterocolitis in this system.