The therapeutic effect of recombinant human trefoil factor 3 on hypoxia-induced necrotizing enterocolitis in immature rat.

Abstract

Trefoil peptides are a new class of regulatory peptides involved in mucosal protection and repair in the gastrointestinal tract. Among them, trefoil factor 3 (TFF3) (intestinal trefoil factor) is known to be cytoprotective in the gut. The aim of this study was to determine the effect of recombinant human trefoil factor 3 (rhTFF3) on hypoxia-induced necrotizing enterocolitis (NEC) in immature rats. In the present study, thirty-two 1-day-old Wistar rat pups were randomly divided into four groups. Group 1 served as nonhypoxic controls. Group 2 rats were subjected to hypoxia reoxygenation (H/O) and then were returned to their mothers. Groups 3 and 4 rats were subjected to H/O, were returned to their mothers, and were treated with rhTFF3 intraperitoneally (0.5 mg) and subcutaneously (0.2 mg), respectively, for the next 3 days. All animals were killed on day 4, and intestine specimens were obtained to determine the histological changes, tissue level of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), malondialdehyde (MDA), prostaglandin E2 (PGE2), tromboxane B2 (TXB2), and nitric oxide (NO). In addition, the effects of rhTFF3 on abundance of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) were also investigated. In neonatal NEC (group 2), necrosis of villi and crypts and, in some cases, transmural necrosis was observed under light microscopy. Tissue level of interleukin-8, tumor necrosis factor-alpha, malondialdehyde, prostaglandin E2, tromboxane B2, and nitric oxide were significantly higher than group 1. In addition, abundance of inducible nitric oxide synthase and cyclooxygenase 2 was markedly increased. In groups 3 and 4, only very slight intestinal injury was observed. The tissue level of interleukin-8, tumor necrosis factor-alpha, malondialdehyde, prostaglandin E2, tromboxane B2, and nitric oxide were significantly decreased in comparison to the group 2. Meanwhile, the abundance of inducible nitric oxide synthase and cyclooxygenase 2 was also marked decreased in comparison to group 2. The current study suggests a therapeutic role of TFF3 in an experimental model of NEC. Our findings may open a new insight into the treatment of NEC in newborns.

• Authors: Bing-Hong Zhang, Hong-Gang Yu, Zhi-Xiang Sheng, He-Sheng Luo, Jie-Ping Yu
• Journal: Regulatory peptides (Regul Pept) Vol. 116 Issue 1-3 Pg. 53-60 (Nov 15 2003) ISSN: 0167-0115 [Print] Netherlands
• PMID: 14599715 (Publication Type: Journal Article)

Chemical References

• Isoenzymes
• Membrane Proteins
• Mucins
• Muscle Proteins
• Peptides
• TFF3 protein, human
• Trefoil Factor-3
• NOS2 protein, human
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases

Topics

• Aging (physiology)
• Animals
• Cyclooxygenase 2
• Enterocolitis, Necrotizing (complications, drug therapy, metabolism, pathology)
• Gene Expression Regulation (drug effects)
• Humans
• Hypoxia (complications, metabolism, pathology)
• Immunohistochemistry
• Intestine, Small (drug effects, metabolism, pathology)
• Isoenzymes (metabolism)
• Membrane Proteins
• Mucins (pharmacology, therapeutic use)
• Muscle Proteins (pharmacology, therapeutic use)
• Nitric Oxide Synthase (metabolism)
• Nitric Oxide Synthase Type II
• Peptides
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Rats
• Trefoil Factor-3