G M Ekström1. 1. Dept. of Pharmacology, Preclinical R & D Unit, Astra Draco AB, Lund, Sweden.
Abstract
BACKGROUND: The intention of the present study was to develop a new hapten-based inflammatory bowel disease model in the rat, useful for pharmacologic screening of new substances with anti-inflammatory properties and immunomodulating capacities. It was considered important to avoid the use of an irritating barrier breaker, such as ethanol. METHODS: Dark Agouti rats were skin-sensitized with oxazolone and further challenged intra-rectally with oxazolone dissolved in carmellose sodium (Orabase)/peanut oil. The effects of treatment with budesonide, prednisolone, cyclosporin A, and 5-aminosalicylic acid (5-ASA) were studied. RESULTS: The intra-rectal challenge with oxazolone in sensitized rats induced an inflammation with an increased colon wet weight, pronounced myeloperoxidase (MPO) activity, and hyperemia/ulcerations in the epithelial lining. Improvement was achieved by treatment with budesonide, prednisolone, and cyclosporin A but not with 5-ASA. CONCLUSIONS: The model fulfills the criteria for a fast, reproducible animal model for human colon inflammation, suitable for pharmacologic screening and studies of an immune-driven colon inflammation.
BACKGROUND: The intention of the present study was to develop a new hapten-based inflammatory bowel disease model in the rat, useful for pharmacologic screening of new substances with anti-inflammatory properties and immunomodulating capacities. It was considered important to avoid the use of an irritating barrier breaker, such as ethanol. METHODS: Dark Agouti rats were skin-sensitized with oxazolone and further challenged intra-rectally with oxazolone dissolved in carmellose sodium (Orabase)/peanut oil. The effects of treatment with budesonide, prednisolone, cyclosporin A, and 5-aminosalicylic acid (5-ASA) were studied. RESULTS: The intra-rectal challenge with oxazolone in sensitized rats induced an inflammation with an increased colon wet weight, pronounced myeloperoxidase (MPO) activity, and hyperemia/ulcerations in the epithelial lining. Improvement was achieved by treatment with budesonide, prednisolone, and cyclosporin A but not with 5-ASA. CONCLUSIONS: The model fulfills the criteria for a fast, reproducible animal model for humancolon inflammation, suitable for pharmacologic screening and studies of an immune-driven colon inflammation.
Authors: Valentin Galitovskiy; Jing Qian; Alexander I Chernyavsky; Steve Marchenko; Vivian Gindi; Robert A Edwards; Sergei A Grando Journal: J Immunol Date: 2011-07-22 Impact factor: 5.422
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