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Cimetidine attenuates vinorelbine-induced phlebitis in mice by militating E-selectin expression

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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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Acknowledgments

This study was funded by the National Natural Science Foundation of China (Grant No. 30973593).

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Authors and Affiliations

  1. Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China

    Zhuo Wang, Lijuan Ma, Xuebin Wang, Heping Cai, Jin Huang, Jiyong Liu & Jinhong Hu

  2. Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China

    Dingfeng Su

Authors
  1. Zhuo Wang
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  2. Lijuan Ma
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  3. Xuebin Wang
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  4. Heping Cai
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  5. Jin Huang
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  6. Jiyong Liu
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  7. Jinhong Hu
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  8. Dingfeng Su
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Corresponding authors

Correspondence to Jinhong Hu or Dingfeng Su.

Additional information

Jinhong Hu and Dingfeng Su have contributed equally to this study. They are co-corresponding authors of this paper.

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Wang, Z., Ma, L., Wang, X. et al. Cimetidine attenuates vinorelbine-induced phlebitis in mice by militating E-selectin expression. Cancer Chemother Pharmacol 74, 239–247 (2014). https://doi.org/10.1007/s00280-014-2487-8

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  • DOI: https://doi.org/10.1007/s00280-014-2487-8

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