title: The bisphosphonate alendronate improves the damage associated with trinitrobenzenesulfonic acid-induced colitis in rats.
abstract: OBJECTIVE
  The nitrogen-containing bisphosphonates are drugs used successfully in the treatment of osteoporosis. They act inhibiting farnesyl diphosphate synthase. This mechanism may also produce anti-inflammatory effects. The therapeutic activity of alendronate was tested in vivo using a model of inflammatory bowel disease.
  
  
  METHODS
  The trinitrobenzenesulfonic acid model of colitis in the rat was used. Rats were treated orally with alendronate and its efficacy compared with that of oral sulphasalazine or vehicle, starting 2 h after colitis induction. The status of the animals was assessed 5 days later.
  
  
  RESULTS
  Alendronate treatment (25 or 75 mg kg(-1) day(-1)) resulted in a decrease in the colonic damage score and loss of body weight (at 25 mg kg(-1) day(-1) only). This was associated to a dramatic reduction in the mRNA levels of interleukin 1 beta (IL-1 beta), monocyte chemoattractant protein 1 (MCP-1) and interleukin 1 receptor antagonist (IL-1 ra). The magnitude of the beneficial effect was comparable to that of sulphasalazine (at a 6-20 fold higher dose). Thus sulphasalazine post-treatment reduced the mRNA levels of IL-1 beta/IL-1 ra and MCP-1 to the same extent as alendronate and additionally lowered colonic alkaline phosphatase activity, but failed to affect body weight loss or colonic damage score. Alendronate failed to exert beneficial effects when administered intraperitoneally.
  
  
  CONCLUSIONS
  Oral but not intraperitoneal alendronate significantly protected the colon in experimental rat colitis. Inflammatory bowel disease patients might benefit from exposure to oral alendronate.
authors: Department of Pharmacology, CIBEREHD, School of Pharmacy, University of Granada, Granada, Spain.
authors: I
authors: I
authors: Ballester
authors: A
authors: A
authors: Daddaoua
authors: R
authors: R
authors: López-Posadas
authors: A
authors: A
authors: Nieto
authors: M D
authors: MD
authors: Suárez
authors: A
authors: A
authors: Zarzuelo
authors: O
authors: O
authors: Martínez-Augustin
authors: F
authors: F
authors: Sánchez de Medina
mesh_terms: D000284:Administration, Oral; D019386:Alendronate / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000235:genetics; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects; D007274:Injections, Intraperitoneal; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012460:Sulfasalazine / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D050071:Bone Density Conservation Agents; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D004164:Diphosphonates; D005765:Gastrointestinal Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D012460:Sulfasalazine; D014302:Trinitrobenzenesulfonic Acid; D019386:Alendronate