title: Comparison of the endothelial toxicity induced by short-term amiodarone and diazepam exposure in a human umbilical vein endothelial cell line (EVC304).
abstract: BACKGROUND
  Venous irritation is the most common side effect of intravenous therapy. Although many in vitro models have been developed to evaluate intravenous drug irritation, these models are not widely accepted.
  
  
  OBJECTIVE
  The aim of this paper is to determine whether delayed or immediate cytotoxicity better reflects the in vivo venous irritation ranking.
  
  
  METHODS
  We compared the endothelial toxicity induced by high-concentrations of amiodarone and diazepam after short-term exposure (20 min) in a human umbilical vein endothelial cell line (EVC304) by using five in vitro models: lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G6PD), glutathione (GSH), adenosine triphosphate (ATP), and MTT assays.
  
  
  RESULTS
  In the 24-h MTT assay, the IC50 of diazepam and amiodarone was 1.08 and 1.96 mM, respectively. In the 48-h MTT assay, the IC50 of diazepam and amiodarone was 1.114 and 1.128 mM, respectively. In the intracellular LDH and G6PD assays, the EC50 of diazepam was found to be 3.307 and 1.53 mM, while the values of amiodarone were 0.853 and 0.325 mM, respectively. In the intracellular ATP and GSH assays, the EC50 of diazepam was 0.905 and 1.283 mM, while the values of amiodarone were 0.040 and 0.326 mM, respectively.
  
  
  CONCLUSIONS
  Both the results of intracellular macromolecule activities and micromolecule concentrations were similar to that observed in in vivo venous irritation studies. However, the delayed cytotoxicity rank from the MTT assay is inconsistent with the in vivo venous irritation rank, suggesting that initial toxicity, but not the delayed toxicity, is related to venous irritation.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China and.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.forename: Runlan
authors.initials: R
authors.lastname: Cai
authors.forename: Chuanjie
authors.initials: C
authors.lastname: Zong
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Qi
mesh_terms: D000638:Amiodarone / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D003975:Diazepam / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans
chemical_list: D000638:Amiodarone; D003975:Diazepam
keywords: Adenosine triphosphate; glucose-6-phosphate dehydrogenase; glutathione; lactate dehydrogenase; venous irritation