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Eur J Pediatr Surg 2016; 26(01): 047-053
DOI: 10.1055/s-0035-1559886
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Effect of N-Acetylserotonin on Intestinal Recovery Following Intestinal Ischemia–Reperfusion Injury in a Rat

Yoav Ben Shahar
1   Department of Surgery, Carmel Medical Center, Haifa, Israel
3   Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
*   The authors contributed equally to the article.
,
Igor Sukhotnik
2   Department of Pediatric Surgery, Bnai Zion Medical Center, Haifa, Israel
3   Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
*   The authors contributed equally to the article.
,
Nir Bitterman
3   Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
,
Yulia Pollak
3   Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
,
Jacob Bejar
4   Department of Pathology, Bnai Zion Medical Center, Haifa, Israel
,
Dmitriy Chepurov
4   Department of Pathology, Bnai Zion Medical Center, Haifa, Israel
,
Arnold Coran
5   Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor, Michigan, United States
,
Arie Bitterman
1   Department of Surgery, Carmel Medical Center, Haifa, Israel
› Author Affiliations
Further Information

Publication History

25 May 2015

22 June 2015

Publication Date:
17 September 2015 (online)

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Abstract

Objective N-acetylserotonin (NAS) is a naturally occurring chemical intermediate in the biosynthesis of melatonin. Extensive studies in various experimental models have established that treatment with NAS significantly protects heart and kidney injury from ischemia–reperfusion (IR). The purpose of the present study was to examine the effect of NAS on intestinal recovery and enterocyte turnover after intestinal IR injury in rats.

Methods Male Sprague–Dawley rats were divided into 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 30 minutes, followed by 48 hours of reperfusion, and (4) IR–NAS rats underwent IR and were treated with IP NAS (20 mg/kg) immediately before abdominal closure. Intestinal structural changes, Park injury score, enterocyte proliferation, and enterocyte apoptosis were determined 24 hours following IR. The expression of Bax, Bcl-2, p-ERK, and caspase-3 in the intestinal mucosa was determined using real-time polymerase chain reaction, Western blot, and immunohistochemistry. A nonparametric Kruskal–Wallis analysis of variance test was used for statistical analysis with p less than 0.05 considered statistically significant.

Results Treatment with NAS resulted in a significant increase in mucosal weight in jejunum and ileum, villus height in the ileum, and crypt depth in jejunum and ileum compared with IR animals. IR–NAS rats also had a significantly proliferation rates as well as a lower apoptotic index in jejunum and ileum which was accompanied by higher Bcl-2 levels compared with IR animals.

Conclusions Treatment with NAS prevents gut mucosal damage and inhibits programmed cell death following intestinal IR in a rat.

Keywords

ischemia–reperfusion - intestine - N-acetylserotonin - cell proliferation - cell apoptosis
 

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