title: Effect of Chelerythrine on Intestinal Cell Turnover following Intestinal Ischemia-Reperfusion Injury in a Rat Model.
abstract: BackgroundChelerythrine (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.MethodsMale 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.ResultsTreatment 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.ConclusionsTreatment with CHE inhibits programmed cell death and prevents intestinal mucosal damage following intestinal IR in a rat.
authors: The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Laboratory of Intestinal Adaptation and Recovery, Haifa, Israel.
authors: Igor
authors: I
authors: Sukhotnik
authors: Department of Pediatric Surgery Bnai Zion Medical Center, Haifa, Israel.
authors: Sivan
authors: S
authors: Bitterman
authors: Department of Surgery, Carmel Medical Center, Technion-Israel Institute of Technology, Haifa, Israel.
authors: Yoav Ben
authors: YB
authors: Shahar
authors: The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Laboratory of Intestinal Adaptation and Recovery, Haifa, Israel.
authors: Yulia
authors: Y
authors: Pollak
authors: Department of Pediatric Surgery Bnai Zion Medical Center, Haifa, Israel.
authors: Nir
authors: N
authors: Bitterman
authors: Department of Emergency Medicine, Carmal Medical Center, Technion-Israel Institute of Technology, Haifa, Israel.
authors: Salim
authors: S
authors: Halabi
authors: Section of Pediatric Surgery, C.S. Mott Children's Hospital and University of Michigan Medical School, Ann Arbor, Michigan, United States.
authors: Arnold G
authors: AG
authors: Coran
authors: Department of Surgery, Carmel Medical Center, Technion-Israel Institute of Technology, Haifa, Israel.
authors: Arie
authors: A
authors: Bitterman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053119:Benzophenanthridines / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D020895:Enterocytes / Q000187:drug effects* / Q000378:metabolism; D007082:Ileum / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D007583:Jejunum / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D053119:Benzophenanthridines; D015415:Biomarkers; D047428:Protein Kinase Inhibitors; C016299:chelerythrine