Triolein emulsion infusion into the hepatic artery increases vascular permeability to doxorubicin in rabbit liver

Abstract

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.