The tight junction disorder plays an important role in the pathological process of many chronic diseases, and is becoming a major concern for the clinical application of metal drugs, i.e. anti-diabetic vanadium compounds. The development of novel tight junction protecting agents has thus been a major research focus. Since oxidative stress is the primary cause for vanadium toxicity, the present work tested the protective effects of zinc gluconate （Zn2＋） alone and when combined with vitamin C （VC） on the vanadium compound （VO（acac）z.）-mediated paracellular leakage of MDCK cells. The experimental results showed that VO（acac）2_ treatment significantly increased the paracellular permeability of MDCK monolayer. Zn2＋ alone showed no protective effects and VC ameliorated tight junction leakage of MDCK cells when given in the basal chamber. Interestingly, unilateral treatment with the combination of Zn2＋ and VC effectively prevented the increase of paracellular permeability. In addition, the combination of zinc and VC down-regulated the levels of reactive oxygen species in both the control and VO（acac）2-treated MDCK cells and caused the elevation of intracellular Ca2＋; both effects were beneficial for the maintenance of integrity of intercellular tight junction. Our results provided a simple but very effective method of preventing the metal toxicity for clinical aoNication of anti-diabetic vanadium compounds.
