The Bisphosphonate Alendronate Improves the Damage Associated with Trinitrobenzenesulfonic Acid-induced Colitis in Rats.
From: Department of Pharmacology, CIBEREHD, School of Pharmacy, University of Granada, Granada, Spain.
British journal of pharmacology
- Publish Date: May 2007
- ISSN: 0007-1188
- Volume: 151
- Issue: 2
- Pages: 206-15
- Medium: Print
- Language: English
- Citation (JAMA): Ballester I, Daddaoua A, López-Posadas R, et al. The Bisphosphonate Alendronate Improves the Damage Associated with Trinitrobenzenesulfonic Acid-induced Colitis in Rats.. Br. J. Pharmacol. May 2007;151:206-15
Abstract
BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY 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 AND IMPLICATIONS: Oral but not intraperitoneal alendronate significantly protected the colon in experimental rat colitis. Inflammatory bowel disease patients might benefit from exposure to oral alendronate.
Mesh Headings (Keywords): Administration, Oral, Alendronate, Animals, Anti-Inflammatory Agents, Body Weight, Bone Density Conservation Agents, Chemokine CCL2, Colitis, Colon, Diphosphonates, Dose-Response Relationship, Drug, Female, Gastrointestinal Agents, Gene Expression, Injections, Intraperitoneal, Interleukin 1 Receptor Antagonist Protein, Interleukin-1beta, Rats, Rats, Wistar, Sulfasalazine, Treatment Outcome, Trinitrobenzenesulfonic Acid
Check for Full Text / PubMed Unique Identifier (PMID): 17375077
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