Cimetidine attenuates vinorelbine-induced phlebitis in mice by militating E-selectin expression.
Cancer Chemother Pharmacol
; 74(2): 239-47, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24879290
ABSTRACT
PURPOSE:
We investigated E-selectin expression in mice and rabbits with vinorelbine-induced phlebitis and the effect of cimetidine. To find the relationship between E-selectin expression and vinorelbine-induced phlebitis.METHODS:
Mouse and rabbit model of vinorelbine-induced phlebitis was established by intravenous infusion of vinorelbine. Pathological observation, molecular-biological determination of E-selectin and protein function of it was evaluated.RESULTS:
Grossly, we observed swelling, edema and cord-like vessel changes in mice receiving vinorelbine but only mild edema in mice pretreated with cimetidine. Pathological scoring yielded a total score of 37 for vinorelbine-treated mice and 17 for mice pretreated with cimetidine (P < 0.05). ELISA revealed that rabbits treated with vinorelbine had markedly higher serum contents of E-selectin than normal saline (NS) controls (vinorelbine 1.534 ± 0.449 vs. NS 0.746 ± 0.170 ng/mL, P < 0.05), which was markedly attenuated by cimetidine (cimetidine 0.717 ± 0.468 vs. vinorelbine 1.534 ± 0.449 ng/mL, P < 0.05). Rose Bengal staining assays showed that vinorelbine markedly increased the adhesion rate of neutrophils for endothelial cells (vinorelbine 38.70 ± 8.34% vs. controls 8.93 ± 4.85%, P < 0.01), which, however, was significantly suppressed by cimetidine (9.93 ± 5.91%, P < 0.01 vs. vinorelbine). In E-selectin knockout mice, we found no apparent difference in tail swelling in mice receiving vinorelbine or cimetidine and vinorelbine.CONCLUSIONS:
In conclusion, cimetidine attenuates vinorelbine-induced phlebitis in mice probably by suppressing increased expression of E-selectin.
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Base de dados:
MEDLINE
Assunto principal:
Flebite
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Vimblastina
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Cimetidina
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Selectina E
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Antagonistas dos Receptores H2 da Histamina
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Antineoplásicos Fitogênicos
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article