Yoav Ben Shahar1, Igor Sukhotnik2, Nir Bitterman3, Yulia Pollak3, Jacob Bejar4, Dmitriy Chepurov4, Arnold Coran5, Arie Bitterman1. 1. Department of Surgery, Carmel Medical Center, Haifa, Israel. 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. 4. Department of Pathology, Bnai Zion Medical Center, Haifa, Israel. 5. Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor, Michigan, United States.
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. Georg Thieme Verlag KG Stuttgart · New York.
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-NASrats 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-NASrats 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-NASrats 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. Georg Thieme Verlag KG Stuttgart · New York.
Authors: I Sukhotnik; N Nissimov; Y Ben Shahar; D Moati; N Bitterman; Y Pollak; D Berkowitz; A G Coran; A Bitterman Journal: Pediatr Surg Int Date: 2016-09-20 Impact factor: 1.827