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

The permeation and cytotoxicity of three insulinmimetic 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 apparent permeation coefficients (Papp) were estimated to be (7.5±1.0)×10−6, (1.0 ± 0.2) ×10−6, (1.7±0.4)×10−6 cm/s for V(V), V(IV), and V(III)-dipic complexes, respectively. The permeability of V(V)-dipic complexes is much better than the others, 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 vanadium 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.