OBJECTIVE: In the current study of murine colitis, the potential roles of thromboxane and the thromboxane-prostanoid (TP) receptor were investigated, in as much as thromboxane signaling has been implicated in human inflammatory bowel disease. METHODS: Colitis was induced in C57BL/6 mice via ingestion of dextran sodium sulfate (DSS), with or without co-administration of the thromboxane synthase inhibitor ozagrel (25 mg/kg/day) or the TP receptor antagonist vapiprost (2.5 mg/kg/day). RESULTS: Immunohistochemistry of colonic tissue demonstrated a DSS-induced increase in TP receptor expression, but not of thromboxane synthase. Moreover, tissue levels of the metabolite thromboxane B(2) were unchanged by DSS. Vapiprost, but not ozagrel, partially attenuated histologic signs of inflammation induced by DSS, with vapiprost allowing a smaller increase in colon weight per unit length than ozagrel. Vapiprost also tended to attenuate DSS-induced alterations in intestinal transit. CONCLUSIONS: In summary, TP receptor antagonism was more effective than thromboxane synthase inhibition in alleviating DSS-induced colitis in mice.
OBJECTIVE: In the current study of murinecolitis, the potential roles of thromboxane and the thromboxane-prostanoid (TP) receptor were investigated, in as much as thromboxane signaling has been implicated in humaninflammatory bowel disease. METHODS:Colitis was induced in C57BL/6 mice via ingestion of dextran sodium sulfate (DSS), with or without co-administration of the thromboxane synthase inhibitor ozagrel (25 mg/kg/day) or the TP receptor antagonist vapiprost (2.5 mg/kg/day). RESULTS: Immunohistochemistry of colonic tissue demonstrated a DSS-induced increase in TP receptor expression, but not of thromboxane synthase. Moreover, tissue levels of the metabolite thromboxane B(2) were unchanged by DSS. Vapiprost, but not ozagrel, partially attenuated histologic signs of inflammation induced by DSS, with vapiprost allowing a smaller increase in colon weight per unit length than ozagrel. Vapiprost also tended to attenuate DSS-induced alterations in intestinal transit. CONCLUSIONS: In summary, TP receptor antagonism was more effective than thromboxane synthase inhibition in alleviating DSS-induced colitis in mice.
Authors: Thorsten Vowinkel; Mikiji Mori; Christian F Krieglstein; Janice Russell; Fumito Saijo; Sulaiman Bharwani; Richard H Turnage; W Sean Davidson; Patrick Tso; D Neil Granger; Theodore J Kalogeris Journal: J Clin Invest Date: 2004-07 Impact factor: 14.808
Authors: L A Dieleman; M J Palmen; H Akol; E Bloemena; A S Peña; S G Meuwissen; E P Van Rees Journal: Clin Exp Immunol Date: 1998-12 Impact factor: 4.330
Authors: T Tanaka; Y Fukuta; R Higashino; R Sato; Y Nomura; Y Fukuda; S Ito; M Takei; T Kurimoto; H Tamaki Journal: Eur J Pharmacol Date: 1998-09-11 Impact factor: 4.432
Authors: K Sato; S Ohkura; Y Kitahara; T Ohama; M Hori; M Sato; S Kobayashi; Y Sasaki; T Hayashi; T Nasu; H Ozaki Journal: Neurogastroenterol Motil Date: 2007-06 Impact factor: 3.598