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

Abstract

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.