title: The antiprotozoal drug pentamidine ameliorates experimentally induced acute colitis in mice.
abstract: BACKGROUND
  Intestinal inflammation is partly driven by enteroglial-derived S100B protein. The antiprotozoal drug pentamidine directly blocks S100B activity. We aimed to investigate the effect of pentamidine on intestinal inflammation using an animal model of dextran sodium sulphate (DSS)-induced acute colitis.
  
  
  METHODS
  Mice were divided into: control group, colitis group (4% DSS for four days) and two pentamidine-treated colitis groups (0.8 mg/kg and 4 mg/kg). Anti-inflammatory effect of pentamidine was assessed in colonic tissue by evaluating the disease activity index and the severity of histological changes. Colonic tissue were also used to evaluate cyclooxigenase-2, inducible nitric oxide synthase, S100B, glial fibrillary acidic protein, phosphorylated-p38 MAPkinase, p50, p65 protein expression, malondyaldheyde production, mieloperoxidase activity, and macrophage infiltration. Nitric oxide, prostaglandin E2, interleukin-1 beta, tumor necrosis factor alpha, and S100B levels were detected in plasma samples. Parallel measurements were performed in vitro on dissected mucosa and longitudinal muscle myenteric plexus (LMMP) preparations after challenge with LPS + DSS or exogenous S100B protein in the presence or absence of pentamidine.
  
  
  RESULTS
  Pentamidine treatment significantly ameliorated the severity of acute colitis in mice, as showed by macroscopic evaluation and histological/biochemical assays in colonic tissues and in plasma. Pentamidine effect on inflammatory mediators was almost completely abrogated in dissected mucosa but not in LMMP.
  
  
  CONCLUSIONS
  Pentamidine exerts a marked anti-inflammatory effect in a mice model of acute colitis, likely targeting S100B activity. Pentamidine might be an innovative molecule to broaden pharmacological tools against colitis.
authors.affiliation: Department of Physiology and Pharmacology 'Vittorio Erspamer', University SAPIENZA of Rome, P le Aldo Moro 5, 00185 Rome, Italy. giuseppe.esposito@uniroma1.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Esposito
authors.forename: Elena
authors.initials: E
authors.lastname: Capoccia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sarnelli
authors.forename: Caterina
authors.initials: C
authors.lastname: Scuderi
authors.forename: Carla
authors.initials: C
authors.lastname: Cirillo
authors.forename: Rosario
authors.initials: R
authors.lastname: Cuomo
authors.forename: Luca
authors.initials: L
authors.lastname: Steardo
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D003092:Colitis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D015232:Dinoprostone / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects; D053583:Interleukin-1beta / Q000097:blood; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D009092:Mucous Membrane / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009573:Nitrites / Q000097:blood; D010419:Pentamidine / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D053583:Interleukin-1beta; D009419:Nerve Tissue Proteins; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D010419:Pentamidine; D016264:Dextran Sulfate; D009195:Peroxidase; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone