Mast Cell Stabilizer Ketotifen [4-(1-Methyl-4-piperidylidene)-4 H-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9 H)-one Fumarate] Prevents Mucosal Mast Cell Hyperplasia and Intestinal Dysmotility in Experimental Trichinella spiralis Inflammation in the Rat
Open Access
- 1 December 2006
- journal article
- Published by Elsevier in The Journal of Pharmacology and Experimental Therapeutics
- Vol. 319 (3) , 1104-1111
- https://doi.org/10.1124/jpet.106.104620
Abstract
Trichinella spiralis infection in rats induces hypermotility and an abnormal response to cholecystokinin (CCK) similar to motor disturbances observed in irritable bowel syndrome. Mast cell hyperplasia is also characteristic of this experimental model. The aim of our study was to correlate mast cell activity with the development of dysmotility and to demonstrate whether the mast cell stabilizer ketotifen [4-(1-methyl-4-piperidylidene)-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one fumarate] could prevent the development of intestine hypermotility. Sprague-Dawley rats were infected with T. spiralis and, 5 days after infection, treated with the mast-cell stabilizer ketotifen (10 mg/kg/day). Twelve days after infection, intestinal spontaneous motor activity and response to CCK were evaluated by means of strain-gauge transducers. Immunohistochemistry for rat mast cell protease II (RMCPII), cyclooxygenase (COX)-2, and inducible nitric-oxide synthase (iNOS) was performed in intestinal specimens. In addition, RMCPII and myeloperoxidase were determined in serum. Infected control rats showed hypermotility, mast cell hyperplasia, increased RMCPII levels, increased myeloperoxidase, and overexpression of COX-2 and iNOS. In contrast, ketotifen-treated rats showed spontaneous intestinal motility and CCK response similar to the noninfected control rats. Mast cell hyperplasia and RMCPII were reduced in ketotifen-treated rats. Inflammatory parameters were less modified by ketotifen, but those animals that received the longest ketotifen treatment showed a slight amelioration in these parameters. These results indicate that mast cells are implicated in the development of hypermotility. The treatment with ketotifen prevented hypermotility and mast cell hyperplasia and diminished mucosal mast cell activity.Keywords
This publication has 49 references indexed in Scilit:
- Mechanisms Underlying the Maintenance of Muscle Hypercontractility in a Model of Postinfective Gut DysfunctionGastroenterology, 2005
- Mast cells in the development of adaptive immune responsesNature Immunology, 2005
- Visceral hyperalgesia and intestinal dysmotility in a mouse model of postinfective gut dysfunctionGastroenterology, 2004
- Comparison of ketotifen fumarate ophthalmic solution alone, desloratadine alone, and their combination for inhibition of the signs and symptoms of seasonal allergic rhinoconjunctivitis in the conjunctival allergen challenge model: a double-masked, placebo- and active-controlled trialPublished by Elsevier ,2003
- Intestinal inflammation and activation of sensory nerve pathways: a functional and morphological study in the nematode infected ratGut, 2001
- Colonic Motility Abnormality in Patients With Irritable Bowel Syndrome Exhibiting Abdominal Pain and DiarrheaAmerican Journal of Gastroenterology, 2001
- Influence of IgE-mediated activation of cultured human mast cells on proliferation and type I collagen production by human dermal fibroblastsJournal of Allergy and Clinical Immunology, 2000
- Alterations of intestinal motor responses to various stimuli after Nippostrongylus brasiliensis infection in rats: role of mast cellsNeurogastroenterology & Motility, 2000
- Ketotifen ameliorates capsaicin-augmented acetic acid-induced colitisDigestive Diseases and Sciences, 1995
- Trichinella spiralis infection alters small bowel motor activity in the fed stateGastroenterology, 1991