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1.
J Pediatr Surg ; 46(3): 489-95, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21376198

ABSTRACT

BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Although ω-3 fatty acids are known to have antiinflammatory effects, their effect against NEC remains unclear. METHODS: Mother rats fed a soybean-based, docosahexaenoic acid (DHA)- or eicosapentaenoic acid (EPA)-enriched diet from days 7 to 20 of gestation were examined. On day 20, the rat pups were delivered by abdominal incision, their intestines were removed, and messenger RNA was extracted. A rat NEC model was used to confirm the effects of ω-3 fatty acids on the inflamed intestine (n = 20-28). The expression of inflammatory molecules was analyzed by real-time polymerase chain reaction (n = 11-14). RESULTS: The concentrations of DHA and EPA in the intestine were significantly increased in the DHA and EPA groups (P < .01). The expression of the antiinflammatory prostaglandin E2 receptor EP3 was increased in the DHA (P < .05) and EPA groups (P < .01). In the NEC model, the reduced incidence of colitis was confirmed in the DHA and EPA groups. The expression of peroxisome proliferator-activated receptor γ was increased (P < .05), and the inhibitor of nuclear factor-κB α/ß decreased in both the DHA (P < .01) and EPA groups (P < .05). CONCLUSION: Our findings indicate that ω-3 fatty acids are beneficial for protecting the premature intestine from inflammation by regulating eicosanoid- and nuclear factor-κB-related metabolite expression.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Dietary Fats, Unsaturated/therapeutic use , Docosahexaenoic Acids/therapeutic use , Eicosapentaenoic Acid/therapeutic use , Enterocolitis, Necrotizing/prevention & control , Animals , Animals, Newborn , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Dietary Fats, Unsaturated/administration & dosage , Disease Models, Animal , Docosahexaenoic Acids/administration & dosage , Docosahexaenoic Acids/pharmacology , Drug Evaluation, Preclinical , Eicosapentaenoic Acid/administration & dosage , Eicosapentaenoic Acid/pharmacology , Enterocolitis, Necrotizing/chemically induced , Fatty Acids/analysis , Female , Gene Expression Regulation/drug effects , Ileum/chemistry , Ileum/drug effects , Ileum/embryology , Infant Food/toxicity , Intestinal Mucosa/drug effects , Maternal-Fetal Exchange , Models, Animal , NF-kappa B/drug effects , PPAR gamma/biosynthesis , PPAR gamma/genetics , Pregnancy , Random Allocation , Rats , Rats, Sprague-Dawley , Receptors, Prostaglandin E, EP3 Subtype/biosynthesis , Receptors, Prostaglandin E, EP3 Subtype/genetics , Soybean Oil , Specific Pathogen-Free Organisms
2.
Neonatology ; 97(3): 218-24, 2010.
Article in English | MEDLINE | ID: mdl-19887849

ABSTRACT

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-kappaB (IkappaB)-alpha/beta and peroxisome proliferator-activated receptor (PPAR)-gamma 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 IkappaB-alpha/beta and PPAR-gamma mRNA increased in inflamed intestine. CONCLUSIONS: Increased expression of IkappaB-alpha/beta suggested that the inflammatory mediator nuclear factor-kappaB 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-gamma may possibly regulate further development of enterocolitis in this system.


Subject(s)
Animals, Newborn , Disease Models, Animal , Enterocolitis, Necrotizing/etiology , Infant, Premature, Diseases/pathology , Overnutrition/complications , Rats , Animals , Animals, Suckling , Enterocolitis/etiology , Enterocolitis/pathology , Enterocolitis, Necrotizing/pathology , Female , Humans , I-kappa B Proteins/genetics , I-kappa B Proteins/metabolism , Infant, Newborn , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , NF-KappaB Inhibitor alpha , Overnutrition/pathology , PPAR gamma/genetics , PPAR gamma/metabolism , Pregnancy , Rats, Sprague-Dawley
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