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Fenofibrate reduces intestinal damage and improves intestinal recovery following intestinal ischemia–reperfusion injury in a rat

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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.

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Author notes

    Authors and Affiliations

    1. Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

      I. Sukhotnik, N. Nissimov, Y. Ben Shahar, D. Moati, N. Bitterman & Y. Pollak

    2. Department of Pediatric Surgery B, Bnai Zion Medical Center, 47 Golomb St., P.O.B. 4940, 31048, Haifa, Israel

      I. Sukhotnik & N. Nissimov

    3. Department of Surgery, Carmel Medical Center, Haifa, Israel

      Y. Ben Shahar & A. Bitterman

    4. Department of Pediatric Gastroenterology, Bnai Zion Medical Center, Haifa, Israel

      D. Berkowitz

    5. Section of Pediatric Surgery, C.S. Mott Children’s Hospital, University of Michigan Medical School, Ann Arbor, MI, USA

      A. G. Coran

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    1. I. Sukhotnik
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    Correspondence to I. Sukhotnik.

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    I. Sukhotnik and N. Nissimov contributed equally to this work.

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    Sukhotnik, I., Nissimov, N., Ben Shahar, Y. et al. Fenofibrate reduces intestinal damage and improves intestinal recovery following intestinal ischemia–reperfusion injury in a rat. Pediatr Surg Int 32, 1193–1200 (2016). https://doi.org/10.1007/s00383-016-3979-x

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    • DOI: https://doi.org/10.1007/s00383-016-3979-x

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