title: Local toxicity of hepatic arterial infusion of hexokinase II inhibitor, 3-bromopyruvate: In vivo investigation in normal rabbit model.
abstract: OBJECTIVE
  3-Bromopyruvate (3-BrPA), an hexokinase II inhibitor, is known to have high necrotic rate in hyperglycolytic liver tumor models without apparent damage to the normal liver parenchyma. The toxicity of intra-arterial delivery of 3-BrPA in various concentrations has not been specifically investigated using a normal rabbit model.
  
  
  METHODS
  Twenty rabbits treated with intra-arterial 3-BrPA were divided into four groups according to its dose and infusion level: 1 mM at the left hepatic artery (group I), 5 mM at the left hepatic artery (group II), 25 mM at the left hepatic artery (group III), and 25 mM at the common hepatic artery (group IV). After selective catheterization, 30 ml of 3-BrPA was infused for 2 minutes. As a control group, five rabbits were treated with normal saline. During 1-week follow-up, toxicities were evaluated with blood laboratory results, mortality, and histopathologic examination.
  
  
  RESULTS
  All 10 rabbits treated with 25 mM 3-BrPA and 2 rabbits treated with 5 mM 3-BrPA died within 3 days after treatment. In 10 of the 12 deaths, hemorrhagic pyloric or duodenal necrosis was noted. Hepatotoxicities on blood laboratory results were dose dependent but transient in the surviving rabbits.
  
  
  CONCLUSIONS
  Selective intra-arterial administration of 25 mM 3-BrPA can cause considerable toxicities not only in the liver but also in the gastrointestinal system and are dose dependent and can cause death in high doses.
authors.affiliation: Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Chang
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Chung
authors.forename: Hwan Jun
authors.initials: HJ
authors.lastname: Jae
authors.forename: Hong
authors.initials: H
authors.lastname: Eh
authors.forename: Kyu Ri
authors.initials: KR
authors.lastname: Son
authors.forename: Ki Chang
authors.initials: KC
authors.lastname: Lee
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000633:toxicity*; D006499:Hepatic Artery; D006593:Hexokinase / Q000037:antagonists & inhibitors*; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000187:drug effects; D011773:Pyruvates / Q000008:administration & dosage* / Q000633:toxicity*; D011817:Rabbits
chemical_list: D004791:Enzyme Inhibitors; D011773:Pyruvates; C017092:bromopyruvate; D006593:Hexokinase