In vivo distribution of arsenic after i.p. injection of arsonoliposomes in balb-c mice

被引:25
作者
Antimisiaris, SG [1 ]
Klepetsanis, P
Zachariou, V
Giannopoulou, E
Ioannou, PV
机构
[1] Lab Pharmaceut Technol, Dept Pharm, Rion 26500, Greece
[2] Sch Med, Dept Pharmacol, Rion 26500, Greece
[3] Univ Patras, Dept Chem, Rion 26500, Greece
关键词
liposome; arsenate; arsenic; distribution; tissue; mice; in vivo; toxicity;
D O I
10.1016/j.ijpharm.2004.11.002
中图分类号
R9 [药学];
学科分类号
1007 [药学];
摘要
We recently showed that arsonoliposomes (novel arsenic containg liposomes) demonstrate differential toxicity towards various types of cancer and normal cells, in cell culture studies, as well as anti-parasitic activity. In this study, the in-vivo distribution of the active moiety of these vesicles, As, is evaluated. Sonicated arsonoliposomes were prepared using the arsonolipid with palmitic acid acyl chain (C16) mixed with egg-phosphatidyl choline (PC) and cholesterol (Chol) [C16/PC/Chol at 8:12:10 mol/mol/mol]. A dose of arsonoliposomes, corresponding to 5 mg arsenate/kg was administered by intraperitoneal injection in balb-c mice. At various time points post-injection the mice were sacrificed and the distribution of As in the organs was measured, by atomic absorption spectroscopy. Results demonstrate that a high portion of the dose administered is rapidly excreted; since 1-h post-injection only about 30% of the dose administered was detected cumulatively in the animal tissues. After this the elimination of arsenic was a slow process with a total body elimination rate constant of 0.023 h(-1), corresponding to a half-life of 30 h. Tissues with the highest arsenic concentration during the study period are: spleen - kidneys - stomach, followed by lung, liver, intestines - heart, carcass + skin and finally blood. No acute toxicity, or effect on the body or organ weight of the mice was observed. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:151 / 158
页数:8
相关论文
共 28 条
[1]
In-vitro antileishmanial and trypanocidal activities of arsonoliposomes and preliminary in-vivo distribution in BALB/c mice [J].
Antimisiaris, SG ;
Ioannou, PV ;
Loiseau, PM .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 2003, 55 (05) :647-652
[2]
The paradox of arsenic: molecular mechanisms of cell transformation and chemotherapeutic effects [J].
Bode, AM ;
Dong, ZG .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2002, 42 (01) :5-24
[3]
DESAULNIERS JAH, 1985, ATOM SPECTROSC, V6, P125
[4]
Determination of lipid-soluble arsenic species in seaweed-eating sheep from Orkney [J].
Devalla, S ;
Feldmann, J .
APPLIED ORGANOMETALLIC CHEMISTRY, 2003, 17 (12) :906-912
[5]
Preparation and properties of arsonolipid containing liposomes [J].
Fatouros, D ;
Gortzi, O ;
Klepetsanis, P ;
Antimisiaris, SG ;
Stuart, MCA ;
Brisson, A ;
Ioannou, PV .
CHEMISTRY AND PHYSICS OF LIPIDS, 2001, 109 (01) :75-89
[6]
Physical stability of sonicated arsonoliposomes: Effect of calcium ions [J].
Fatouros, DG ;
Piperoudi, S ;
Gortzi, O ;
Ioannou, PV ;
Frederik, P ;
Antimisiaris, SG .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2005, 94 (01) :46-55
[7]
Arsonoliposomes: effect of arsonolipid acyl chain length and vesicle composition on their toxicity towards cancer and normal cells in culture [J].
Gortzi, O ;
Antimisiaris, SG ;
Klepetsanis, P ;
Papadimitriou, E ;
Ioannou, PV .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2003, 18 (02) :175-183
[8]
Arsonoliposomes, a novel class of arsenic-containing liposomes: Effect of palmitoyl-arsonolipid-containing liposomes on the viability of cancer and normal cells in culture [J].
Gortzi, O ;
Papadimitriou, E ;
Kontoyannis, CG ;
Antimisiaris, SG ;
Ioannou, PV .
PHARMACEUTICAL RESEARCH, 2002, 19 (01) :79-86
[9]
Gregoriadis G., 1993, LIPOSOME TECHNOLOGY
[10]
Apoptosis and growth inhibition in malignant lymphocytes after treatment with arsenic trioxide at clinically achievable concentrations [J].
Huff, J ;
Waalkes, M ;
Nyska, A ;
Chan, P .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1999, 91 (19) :1690-1691