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Eur J Pediatr Surg 2017; 27(01): 036-043
DOI: 10.1055/s-0036-1587588
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Effect of Chelerythrine on Intestinal Cell Turnover following Intestinal Ischemia-Reperfusion Injury in a Rat Model

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

Publication History

14 May 2016

24 June 2016

Publication Date:
14 August 2016 (online)

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Abstract

Background Chelerythrine (CHE) is a benzophenanthridine alkaloid that is a potent, selective, and cell-permeable protein kinase C inhibitor. The purpose of the present study was to examine the effect of CHE on intestinal recovery and enterocyte turnover after intestinal ischemia-reperfusion (IR) injury in rats.

Methods Male Sprague-Dawley rats were divided into four experimental groups: (1) sham rats underwent laparotomy, (2) sham-CHE rats underwent laparotomy and were treated with intraperitoneal CHE; (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-CHE rats underwent IR and were treated with intraperitoneal CHE 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 Western blot and immunohistochemistry.

Results Treatment with CHE resulted in a significant decrease in Park injury score in jejunum (threefold decrease) and ileum (twofold decrease), and parallel increase in mucosal weight in jejunum and ileum, villus height in jejunum and ileum, and crypt depth in ileum compared with IR animals. IR-CHE rats also experienced a significantly lower apoptotic index in jejunum and ileum, which was accompanied by a lower Bax/Bcl2 ratio compared with IR animals.

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

Keywords

ischemia-reperfusion - intestine - chelerythrine - apoptosis

* The authors Igor Sukhotnik and Sivan Bitterman contributed equally to the article.


 

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