Enhanced activity of a hydrogen sulphide-releasing derivative of mesalamine (ATB-429) in a mouse model of colitis
| Autor: | FIORUCCI S, ORLANDI S, MENCARELLI A, DISTRUTTI E, SANTUCCI L, WALLACE J. L., CALIENDO, GIUSEPPE, SANTAGADA, VINCENZO, CIRINO, GIUSEPPE |
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| Přispěvatelé: | Fiorucci, S, Orlandi, S, Mencarelli, A, Caliendo, Giuseppe, Santagada, Vincenzo, Distrutti, E, Santucci, L, Cirino, Giuseppe, Wallace, J. L. |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Mice
Inbred BALB C Time Factors Dose-Response Relationship Drug Colon Anti-Inflammatory Agents Gene Expression Colitis Research Papers Severity of Illness Index Disease Models Animal Mice coliti Gastrointestinal Agents Trinitrobenzenesulfonic Acid inflammatory bowel disease Animals Cytokines Female Disulfides Hydrogen Sulfide RNA Messenger Chemokines hydrogen sulphide Mesalamine Granulocytes |
| Popis: | Mesalamine is the first-line therapy for colitis, but it lacks potency and is only effective for mild-to-moderate forms of this disease. Hydrogen sulphide has been shown to be a potent, endogenous anti-inflammatory substance, modulating leukocyte-endothelial adhesion and leukocyte migration. The purpose of this study was to determine if an H(2)S-releasing derivative of mesalamine (ATB-429) would exhibit increased potency and effectiveness in a mouse model of colitis.Colitis was induced in mice with trinitrobenzene sulphonic acid and the effects of ATB-429 and mesalamine were compared in several treatment regimens. The severity of colitis was determined using several indices, including a disease activity score (comprised of scores for diarrhea, weight loss and fecal blood), colonic myeloperoxidase activity and macroscopic/microscopic scoring of tissue injury.Irrespective of the treatment regiment, ATB-429 was more effective than mesalamine in reducing the severity of colitis. ATB-429 was particularly effective in reducing granulocyte infiltration into the colonic tissue (by approximately 70%), as well as reducing the expression of mRNA for several key proinflammatory cytokines/chemokines (e.g., TNFalpha, IFNgamma). Treatment with ADT-OH, the H(2)S-releasing moiety of ATB-429, did not affect severity of colitis.ATB-429 exhibits a marked increase in anti-inflammatory activity and potency in a murine model of colitis, as compared to mesalamine. These results are consistent with recently described anti-inflammatory effects of H(2)S. ATB-429 may represent an attractive alternative to mesalamine for the treatment of inflammatory bowel disease. |
| Databáze: | OpenAIRE |
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