Fenofibrate reduces intestinal damage and improves intestinal recovery following intestinal ischemia–reperfusion injury in a rat
Authors: A G Coran
D Moati
N Nissimov
Y Ben Shahar
N Bitterman
A Bitterman
I Sukhotnik
Y Pollak
D Berkowitz
Journal: Pediatric Surgery International (2016)
Discipline: CLINICAL MEDICINE
Keywords: Apoptosis; Fenofibrate; Intestine; Ischemia–reperfusion; Proliferation.
Affiliations: Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. ., Department of Pediatric Surgery B, Bnai Zion Medical Center, 47 Golomb St., P.O.B. 4940, 31048, Haifa, Israel. ., Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel., Department of Pediatric Surgery B, Bnai Zion Medical Center, 47 Golomb St., P.O.B. 4940, 31048, Haifa, Israel., Department of Surgery, Carmel Medical Center, Haifa, Israel., Department of Pediatric Gastroenterology, Bnai Zion Medical Center, Haifa, Israel., Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor, MI, USA.

Abstract:  Purpose: Fenofibrate (FEN) is known as a nuclear receptor activator which regulates many pathophysiological processes, such as oxidative stress, inflammation, and leukocyte endothelium interactions. Recent studies have demonstrated an anti-oxidant, anti-inflammatory, and anti-ischemic role of FEN in the attenuation of ischemia-reperfusion (IR) injury in the kidney, liver, brain, and heart. The purpose of the present study was to examine the effect of FEN 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-FEN rats underwent laparotomy and were treated with intraperitoneal (IP) FEN (20 mg/kg); (3) IR rats underwent occlusion of both the superior mesenteric artery and the portal vein for 30 min followed by 24 h of reperfusion, and (4) IR-FEN rats underwent IR and were treated with IP FEN immediately before abdominal closure. Intestinal structural changes, Park's injury score, enterocyte proliferation, and enterocyte apoptosis were determined 24 h following IR. The expression of Bax, Bcl-2, p-ERK, and caspase-3 in the intestinal mucosa was determined using real-time PCR, Western blot, and immunohistochemistry. Results: Treatment with FEN resulted in a significant decrease in Park's injury score in jejunum (32 %) and ileum (33 %) compared to IR animals. IR-FEN rats also demonstrated a significant increase in mucosal weight in jejunum (23 %) and ileum (22 %), mucosal DNA (38 %) and protein (65 %) in jejunum, villus height in jejunum (17 %) and ileum (21 %), and crypt depth in ileum (14 %) compared to IR animals. IR-FEN rats also experienced significant proliferation rates as well as lower apoptotic indices in jejunum and ileum which was accompanied with higher Bcl-2 levels compared to IR animals. Conclusions: Treatment with fenofibrate prevents intestinal mucosal damage and stimulates intestinal epithelial cell turnover following intestinal IR in a rat model. 

Retracted: No

PubPeer comments:
 This paper appears to be part of a set of at least 18 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 18. Sukhotnik I et al., Pediatric Surgery International (2016), DOI: 10.1007 s00383-016-3979-x (this paper) Here are four collages of the IHC figures from papers 1-17, 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] And here is Figure 2 from this paper, where two panels, marked in light blue and light green, appear to match those in the collages. ![file] ,