Effect of Chelerythrine on Intestinal Cell Turnover following Intestinal Ischemia-Reperfusion Injury in a Rat Model
Authors: Arnold G Coran
Yoav Ben Shahar
Nir Bitterman
Sivan Bitterman
Salim Halabi
Arie Bitterman
Igor Sukhotnik
Yulia Pollak
Journal: European Journal of Pediatric Surgery (2016)
Discipline: CLINICAL MEDICINE
Keywords: Chelerythrine; intestinal recovery; enterocyte turnover; ischemia-reperfusion injury; rats
Affiliations: Department of Pediatric Surgery  Bnai Zion Medical Center, Haifa, Israel, Department of Surgery, Carmel Medical Center, Technion-Israel Institute of Technology, Haifa, Israel, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Laboratory of Intestinal Adaptation and Recovery, Haifa, Israel, Department of Emergency Medicine, Carmal Medical Center, Technion-Israel Institute of Technology, Haifa, Israel, Section of Pediatric Surgery, C.S. Mott Children's Hospital and University of Michigan Medical School, Ann Arbor, Michigan, United States

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. 

Retracted: No

PubPeer comments:
 This paper appears to be part of a set of at least 17 papers that appear to share immunohistochemistry images. All papers list Igor Sukhotnik as an author and they span a period of 14 years. The images do not always represent the same experiments. 1. Sukhotnik I et al., Pediatr Surg Int (2005) 21: 132u2013137, DOI: 10.1007 s00383-004-1308-2 2. Sukhotnik I et al., Journal of Surgical Research (2005), DOI: 10.1016 j.jss.2005.04.032 3. Sukhotnik I et al., Journal of Surgical Research (2007), DOI: 10.1016 j.jss.2007.02.002 4. Mogilner JG et al., Journal of Pediatric Surgery (2007), DOI: 10.1016 j.jpedsurg.2007.03.035 5. Sukhotnik I et al., Dig Dis Sci (2008), DOI: 10.1007 s10620-007-9990-2 6. Sukhotnik I et al., Cancer Biology Therapy (2009), DOI: 10.4161 cbt.8.10.8128 7. Sukhotnik I et al., Journal of Pediatric Surgery (2011), DOI: 10.1016 j.jpedsurg.2010.09.051 8. Ben-Lulu S et al., PLOS ONE (2012), DOI: 10.1371 journal.pone.0045221 9. Koppelman T et al., BMC Gastroenterology (2012), DOI: 10.1186 1471-230X-12-41 10. Koppelman T et al., British Journal of Nutrition (2013), DOI: 10.1017 S0007114512000542 11. Swaid F et al., Nutrition Metabolism (2013), DOI: 10.1186 1743-7075-10-53 12. Sukhotnik I et al., Nutrition Metabolism (2014), DOI: 10.1186 1743-7075-11-17 13. Sukhotnik I et al., PLOS ONE (2014), DOI: 10.1371 journal.pone.0110675 14. Sukhotnik I et al., European Journal of Pediatric Surgery (2016), DOI: 10.1055 s-0036-1587588 15. Ben Shahar Y et al., European Journal of Pediatric Surgery (2016), DOI: 10.1055 s-0035-1559886 16. Sukhotnik I et al., Food Nutrition Research (2018), DOI: 10.29219 fnr.v62.1327 17. Ben-Shahar Y et al., European Journal of Pediatric Surgery (2019), DOI: 10.1055 s-0039-1700550 Here are four collages of the IHC figures from these papers, with boxes of the same color highlighting panels that look more similar than expected. * Collage 1: ![file] * Collage 2: ![file] * Collage 3: ![file] * Collage 4: ![file] ,