Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2021; 27(2): 152-161
Published online Jan 14, 2021. doi: 10.3748/wjg.v27.i2.152
Triolein emulsion infusion into the hepatic artery increases vascular permeability to doxorubicin in rabbit liver
Yong-Woo Kim, Hak Jin Kim, Byung Mann Cho, Seon Hee Choi
Yong-Woo Kim, Department of Radiology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University College of Medicine, Yangsan 50612, South Korea
Hak Jin Kim, Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University College of Medicine, Busan 49241, South Korea
Byung Mann Cho, Preventive Medicine and Occupational Medicine, Pusan National University School of Medicine, Yangsan 50612, South Korea
Seon Hee Choi, Department of Radiology, Pusan National University, Busan 49241, South Korea
Author contributions: Kim YW and Kim HJ designed the research and wrote the paper; Kim YW, Kim HJ and Choi SH performed the research and acquired the data; Cho BM, Kim YW and Kim HJ analyzed and interpreted the data, revised the manuscript critically for important intellectual content and approved the final version for submission.
Supported by Biomedical Research Institute, Pusan National University Hospital, No. 2018B008.
Institutional animal care and use committee statement: Animal experiments were performed according to our Institutional Laboratory Animal Protocol Guidelines (Approval No. PNUH-2019-139).
Conflict-of-interest statement: Hak Jin Kim has received research funding from Pusan National University Hospital.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at Informed consent was not obtained because this study is animal research. No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Hak Jin Kim, PhD, Professor, Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University College of Medicine, 179 Gudeok-ro, Seo-gu, Busan 49241, South Korea.
Received: October 14, 2020
Peer-review started: October 14, 2020
First decision: December 3, 2020
Revised: December 15, 2020
Accepted: December 22, 2020
Article in press: December 22, 2020
Published online: January 14, 2021

The infusion of triolein emulsion (TE) induced increased vascular permeability and a negligible and temporary decrease in liver function without specific histopathological damage.


To assess changes in doxorubicin concentration according to the percentage of TE infused via a hepatic artery to study the vascular permeability in the rabbit liver.


Thirty-nine healthy rabbits were divided into five groups according to the concentration of emulsified triolein infused into the hepatic arteries: Group 0, saline infusion (control group, n = 5); group 1, 0.3% TE (n = 13); group 2, 0.6% TE (n = 6); group 3, 0.9% TE (n = 8); and group 4, 1.5% TE (n = 6). Doxorubicin (2.4 mg/kg) was infused immediately after TE injection via the hepatic arteries. After 2 h, the livers were harvested, and doxorubicin concentrations were calculated fluorometrically. The doxorubicin concentrations were compared between TE groups and the control group, and the optimal concentrations within the TE groups were calculated. Statistical analysis was performed using the nonparametric Mann-Whitney U test and Kruskal–Wallis test. P < 0.05 were considered statistically significant.


In the liver, doxorubicin concentrations were 2.06, 2.07, 2.16 and 1.66 times higher in groups 1 through 4, respectively, and significantly higher in the TE groups than in the control group (all P < 0.05). However, there were no significant differences in the mean doxorubicin concentrations between the four TE groups (P = 0.642). In the lungs, the mean doxorubicin concentrations were not significantly different between the control and TE groups (P > 0.05).


TE infusion into the hepatic arteries significantly increased the doxorubicin concentration approximately twofold but was not different between the TE groups. These findings suggest that TE infusion might be a useful adjuvant treatment of liver cancers.

Keywords: Triolein emulsion, Liver tumor, Chemotherapy, Drug delivery, Vascular permeability, Dexorubicin

Core Tip: Triolein emulsion infused intra-arterially increases vascular permeability transiently and reversibly. This could be applicable for adjuvant treatment to enhance chemotherapy using an angiographic technique. This study assessed changes in doxorubicin concentration per the percentage of TE infused via hepatic arteries to study vascular permeability in rabbit liver.