title: Cimetidine attenuates vinorelbine-induced phlebitis in mice by militating E-selectin expression.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Lijuan
authors.initials: L
authors.lastname: Ma
authors.forename: Xuebin
authors.initials: X
authors.lastname: Wang
authors.forename: Heping
authors.initials: H
authors.lastname: Cai
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.forename: Jiyong
authors.initials: J
authors.lastname: Liu
authors.forename: Jinhong
authors.initials: J
authors.lastname: Hu
authors.forename: Dingfeng
authors.initials: D
authors.lastname: Su
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002927:Cimetidine / Q000627:therapeutic use*; D019040:E-Selectin / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010689:Phlebitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000633:toxicity; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019040:E-Selectin; D006635:Histamine H2 Antagonists; D012333:RNA, Messenger; D014747:Vinblastine; D002927:Cimetidine; D000077235:Vinorelbine