期刊
CANCER CHEMOTHERAPY AND PHARMACOLOGY
卷 74, 期 2, 页码 239-247出版社
SPRINGER
DOI: 10.1007/s00280-014-2487-8
关键词
Cimetidine; Vinorelbine; Infusion-induced phlebitis; E-selectin
资金
- National Natural Science Foundation of China [30973593]
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. 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. 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 +/- A 0.449 vs. NS 0.746 +/- A 0.170 ng/mL, P < 0.05), which was markedly attenuated by cimetidine (cimetidine 0.717 +/- A 0.468 vs. vinorelbine 1.534 +/- A 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 +/- A 8.34 % vs. controls 8.93 +/- A 4.85 %, P < 0.01), which, however, was significantly suppressed by cimetidine (9.93 +/- A 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. In conclusion, cimetidine attenuates vinorelbine-induced phlebitis in mice probably by suppressing increased expression of E-selectin.
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