title: Effect of N-Acetylserotonin on Intestinal Recovery Following Intestinal Ischemia-Reperfusion Injury in a Rat.
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.
authors.affiliation: Department of Surgery, Carmel Medical Center, Haifa, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Ben Shahar
authors.affiliation: Department of Pediatric Surgery, Bnai Zion Medical Center, Haifa, Israel.
authors.forename: Igor
authors.initials: I
authors.lastname: Sukhotnik
authors.affiliation: Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Bitterman
authors.affiliation: Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Pollak
authors.affiliation: Department of Pathology, Bnai Zion Medical Center, Haifa, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Bejar
authors.affiliation: Department of Pathology, Bnai Zion Medical Center, Haifa, Israel.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Chepurov
authors.affiliation: Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor, Michigan, United States.
authors.forename: Arnold
authors.initials: A
authors.lastname: Coran
authors.affiliation: Department of Surgery, Carmel Medical Center, Haifa, Israel.
authors.forename: Arie
authors.initials: A
authors.lastname: Bitterman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D004334:Drug Administration Schedule; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007422:Intestines / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D008297:Male; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D020011:Protective Agents; D012701:Serotonin; C006389:N-acetylserotonin