Local toxicity of hepatic arterial infusion of hexokinase II inhibitor, 3-bromopyruvate: In vivo investigation in normal rabbit model.
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.
Chang
Jung Min
JM
Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea.
Chung
Jin Wook
JW
Jae
Hwan Jun
HJ
Eh
Hong
H
Son
Kyu Ri
KR
Lee
Ki Chang
KC
Park
Jae Hyung
JH
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
D004791:Enzyme Inhibitors; D011773:Pyruvates; C017092:bromopyruvate; D006593:Hexokinase