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Local toxicity of hepatic arterial infusion of hexokinase II inhibitor, 3-bromopyruvate: In vivo investigation in normal rabbit model.

Abstract：

RATIONALE AND OBJECTIVES: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. MATERIALS AND 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. CONCLUSION: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.

journal_name

Acad Radiol

journal_title

Academic radiology

authors

Chang JM,Chung JW,Jae HJ,Eh H,Son KR,Lee KC,Park JH

doi

10.1016/j.acra.2006.09.059

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

85-92

issue

1

eissn

1076-6332

issn

1878-4046

pii

S1076-6332(06)00570-8

journal_volume

14

pub_type

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