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Combination of vitamin C and zinc gluconate prevented vanadium-induced tight junction leakage of MDCK cell monolayer

Zhihan Xu, Xinyi Wang, Ruyue Xiao, Xiaoda Yang*   

  1. 1. State Key Laboratories of Natural and Biomimetic Drugs and Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
    2. SATCM Key Laboratory of Compound Drug Detoxication, Peking University, Beijing 100191, China
  • Received:2013-05-02 Revised:2013-05-15 Online:2013-09-15 Published:2013-09-15
  • Contact: Xiaoda Yang*

Abstract:

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))-mediated paracellular leakage of MDCK cells. The experimental results showed that VO(acac) 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 application of anti-diabetic vanadium compounds.

Key words: Zinc gluconate, Vitamin C, Tight junction, Oxidative damage, Intracellular calcium

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