Eur J Pediatr Surg
DOI: 10.1055/s-0037-1618593
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Effect of N-Acetylserotonin on TLR-4 and MyD88 Expression during Intestinal Ischemia-Reperfusion in a Rat Model

Igor Sukhotnik
Department of Pediatric Surgery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Laboratory of Intestinal Adaptation and Recovery, Bnai Zion Medical Center, Haifa, Israel
,
Yoav Ben Shahar
Department of Surgery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Carmel Medical Center, Haifa, Israel
,
Salim Halabi
Department of Emergency Medicine, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Carmel Medical Center, Haifa, Israel
,
Nir Bitterman
The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Laboratory of Intestinal Adaptation and Recovery, Haifa, Israel
,
Tatiana Dorfman
Department of Pediatric Surgery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Laboratory of Intestinal Adaptation and Recovery, Bnai Zion Medical Center, Haifa, Israel
,
Yulia Pollak
The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Laboratory of Intestinal Adaptation and Recovery, Haifa, Israel
,
Arnold Coran
Section of Pediatric Surgery, C.S. Mott Children's Hospital, Ann Arbor, Michigan, United States
,
Arie Bitterman
Department of Surgery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Carmel Medical Center, Haifa, Israel
› Author Affiliations
Further Information

Publication History

24 May 2017

06 December 2017

Publication Date:
05 January 2018 (eFirst)

Abstract

Background Accumulating evidence indicates that changes in intestinal toll-like receptors (TLRs) precede histological injury in a rodent model of necrotizing enterocolitis. N-acetylserotonin (NAS) is a naturally occurring chemical intermediate in the biosynthesis of melatonin. A recent study has shown that treatment with NAS prevents gut mucosal damage and inhibits programmed cell death following intestinal ischemia-reperfusion (IR). The objective of this study was to determine the effects of NAS on TLR-4, myeloid differentiation factor 88 (Myd88), and TNF-α receptor-associated factor 6 (TRAF6) expression in intestinal mucosa following intestinal IR in a rat.

Methods Male Sprague-Dawley rats were randomly assigned to one of the four experimental groups: 1) Sham rats underwent laparotomy; 2) Sham-NAS rats underwent laparotomy and were treated with intraperitoneal (IP) NAS (20 mg/kg); 3) IR rats underwent occlusion of both superior mesenteric artery and portal vein for 20 minutes followed by 48 hours of reperfusion; and 4) IR-NAS rats underwent IR and were treated with IP NAS immediately before abdominal closure. Intestinal structural changes, mucosal TLR-4, MyD88, and TRAF6 mucosal gene, and protein expression were examined using real-time PCR, Western blot, and immunohistochemistry.

Results Significant mucosal damage in IR rats was accompanied by a significant upregulation of TLR-4, MyD88, and TRAF6 gene and protein expression in intestinal mucosa compared with control animals. The administration of NAS decreased the intestinal injury score, inhibited cell apoptosis, and significantly reduced the expression of TLR-4, MyD88, and TRAF6.

Conclusion Treatment with NAS is associated with downregulation of TLR-4, MyD88, and TRAF6 expression along with a concomitant decrease in intestinal mucosal injury caused by intestinal IR in a rat.