title: Experimental colitis in mice is attenuated by changes in the levels of endocannabinoid metabolites induced by selective inhibition of fatty acid amide hydrolase (FAAH).
abstract: OBJECTIVE
  Pharmacological treatment and/or maintenance of remission in inflammatory bowel diseases (IBD) is currently one of the biggest challenge in the field of gastroenterology. Available therapies are mostly limited to overcoming the symptoms, but not the cause of the disease. Recently, the endocannabinoid system has been proposed as a novel target in the treatment of IBD. Here we aimed to assess the anti-inflammatory action of the novel fatty acid amide hydrolase (FAAH) inhibitor PF-3845 and its effect on the endocannabinoid and related lipid metabolism during the course of experimental colitis.
  
  
  METHODS
  We used two models of experimental colitis in mice (TNBS- and DSS-induced) and additionally, we employed LC/MS/MS spectrometry to determine the changes in biolipid levels in the mouse colon during inflammation.
  
  
  RESULTS
  We showed that the FAAH inhibitor PF-3845 reduced experimental TNBS-induced colitis in mice and its anti-inflammatory action is associated with altering the levels of selected biolipids (arachidonic and oleic acid derivatives, prostaglandins and biolipids containing glycine in the mouse colon).
  
  
  CONCLUSIONS
  We show that FAAH is a promising pharmacological target and the FAAH-dependent biolipids play a major role in colitis. Our results highlight and promote therapeutic strategy based on targeting FAAH-dependent metabolic pathways in order to alleviate intestinal inflammation.
authors: Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors: M
authors: M
authors: Sałaga
authors: Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors: A
authors: A
authors: Mokrowiecka
authors: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors: P K
authors: PK
authors: Zakrzewski
authors: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors: A
authors: A
authors: Cygankiewicz
authors: Department of Psychological and Brain Sciences, Gill Center for Biomolecular Science, Indiana University, Bloomington, IN, USA.
authors: E
authors: E
authors: Leishman
authors: Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors: M
authors: M
authors: Sobczak
authors: Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors: H
authors: H
authors: Zatorski
authors: Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors: E
authors: E
authors: Małecka-Panas
authors: Department of Pathology, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors: R
authors: R
authors: Kordek
authors: Department of Medicine, Division of Gastroenterology, Ludwig Maximilians University of Munich, Munich, Germany.
authors: M
authors: M
authors: Storr
authors: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors: W M
authors: WM
authors: Krajewska
authors: Department of Psychological and Brain Sciences, Gill Center for Biomolecular Science, Indiana University, Bloomington, IN, USA.
authors: H B
authors: HB
authors: Bradshaw
authors: Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland. Electronic address: jakub.fichna@umed.lodz.pl.
authors: J
authors: J
authors: Fichna
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002186:Cannabinoids / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D002186:Cannabinoids; D007211:Indoles; D010880:Piperidines; D011720:Pyrazoles; D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases; C557973:PF 3845; C103505:AM 251; C094023:iodopravadoline
keywords: Experimental colitis; Fatty acid amide hydrolase;; Inflammatory bowel diseases;; Intestinal inflammation;; PF-3845;