Indomethacin-induced small intestinal injury is ameliorated by cilostazol, a specific PDE-3 inhibitor.
Scand J Gastroenterol
; 47(8-9): 993-1002, 2012 Sep.
Article
em En
| MEDLINE
| ID: mdl-22934593
ABSTRACT
BACKGROUND:
Neutrophil migration, one of the major factors predisposing to nonsteroidal anti-inflammatory drugs (NSAIDs)-induced intestinal lesions, consists of several steps, including interaction with P-selectin from platelets. Cilostazol, a specific phosphodiesterase (PDE)-3 inhibitor, suppresses the expression of P-selectin from platelets and reduces interaction between platelets and leukocytes, leading to inflammatory amelioration in several disease models. We tried to clarify the therapeutic effectiveness of cilostazol for NSAID-induced small intestinal lesions. SUBJECTS ANDMETHODS:
1) Anti-PSGL-1 antibody (2 mg/kg) or cilostazol (100 mg/kg) was administered to mice one hour before Indomethacin (IND, 2.5 mg/kg) administration for 4 days to evaluate small intestinal lesions. 2) IND-induced migratory behaviors of neutrophils and platelets were evaluated in intestinal vessels by an intravital microscopy.RESULTS:
i) IND induced small intestinal lesions with an increase in MPO activity. Anti-PSGL-1 antibody and cilostazol ameliorated intestinal lesions along with suppression of MPO activity. ii) Intravital microscopy revealed that administration of IND increased migration of platelet-bearing neutrophils. Cilostazol treatment ameliorated neutrophil migration by blocking interaction between platelets and neutrophils.CONCLUSION:
Our results suggest that enhanced platelets-bearing neutrophil migration is critically involved in the pathogenesis of IND-induced small intestinal lesions and suggest a potential application of cilostazol for prevention of NSAID-induced small intestinal lesions.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tetrazóis
/
Anti-Inflamatórios não Esteroides
/
Indometacina
/
Inibidores da Fosfodiesterase 3
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Doenças do Íleo
/
Íleo
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Scand J Gastroenterol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Japão