Permeation of vanadium(III,IV,V)-dipicolinate complexes across MDCK cell monolayer and comparison with Caco-2 cells  

作　　者：ZHANG Yue YANG Xiaoda WANG Kui 

机构地区：[1]Department of Chemical Biology, Laboratory of Preventive Pharmaceutics, School of Pharmaceutical Science, Peking University, Beijing 100083, China [2]National Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Science, Peking University, Beijing 100083, China

出　　处：《Chinese Science Bulletin》2005年第17期1854-1859,共6页

摘　　要：The permeation and cytotoxicity of three insu-lin-mimetic vanadium(III, IV, V)-dipicolinate complexes were studied using the MDCK cell monolayer in comparison with the Caco-2 cells. On MDCK cell monolayer, the appar-ent permeation coefficients (Papp) were estimated to be (7.5 ± 1.0)×10?6, (1.0 ± 0.2)×10?6, (1.7±0.4)×10?6 cm/s for V(V), V(IV), and V(III)-dipic complexes, respectively. The perme-ability of V(V)-dipic complexes is much better than the oth-ers, which is in agreement with its better hypoglycemic effect in animal tests. On Caco-2 cell monolayer, Papp were found to be in the range of 1-3×10?6 cm/s and not to be affected by excessive amounts of dipicolinate ligand. By contrast, the permeability in the AP→BL direction across the MDCK monolayer increased greatly in the presence of free ligands, suggesting existence of active transport mechanism of vana-dium complex anions on the MDCK cells. The cytotoxicity of the three complexes was found similar and the IC50 were measured in the range of 0.6―0.9 mmol/L for MDCK cells and 1.6―2 mmol/L for Caco-2 cells. The cytotoxicity of three vanadium complexes was conceivably in consistence with their permeability, suggesting that the toxicity, permeation and cellular metabolism of vanadium complexes are closely related.The permeation and eytotoxicity of three insulin-mimetic vanadium（Ⅲ, Ⅳ, Ⅴ）-dipicolinate complexes were studied using the MDCK cell monolayer in comparison with the Caeo-2 cells. On MDCK cell monolayer, the apparent permeation coefficients （Papp） were estimated to be （7.5±1.0）×10^-6, （1.0±0.2）×10^-6, （1.7±0.4）× 10^-6cm/s for V（Ⅴ）, V（Ⅵ）, and V（Ⅲ）-dipie complexes, respectively. The permeability of V（Ⅴ）-dipie complexes is much better than the others, which is in agreement with its better hypoglycemie effect in animal tests. On Caeo-2 cell monolayer, Papp were found to be in the range of 1-3×10^-6 ends and not to be affected by excessive amounts of dipieolinate ligand. By contrast, the permeability in the AP→BL direction across the MDCK monolayer increased greatly in the presence of free ligands, suggesting existence of active transport mechanism of vanadium complex anions on the MDCK cells. The eytotoxieity of the three complexes was found similar and the IC50 were measured in the range of 0.6-0.9 mmol/L for MDCK cells and 1.6--2 mmol/L for Caco-2 cells. The cytotoxicity of three vanadium complexes was conceivably in consistence with their permeability, suggesting that the toxicity, permeation and cellular metabolism of vanadium complexes are closely related.

关 键 词：矾化合物 MDCK 肠吸收 糖尿病 细胞单层 

分 类 号：R587.1[医药卫生—内分泌]