Inhibitory effects of zinc chloride (ZnCl2), n-acetyl-L-cysteine (NAC), and calcium/calmodulin dependent protein kinase II inhibitor (KN93) on Cd2+-induced abnormal cell morphology and membrane permeability

Abstract

Cadmium (Cd) could reduce abnormal cell morphology and membrane permeability, however, there are few studies on the detoxification of Cd-reduced cell membrane toxicity. In the present study, we firstly studied the effects of zinc chloride (ZnCl2), n-acetyl-L-cysteine (NAC), and calcium/calmodulin dependent protein kinase II inhibitor (KN93) on cell membrane permeability, respectively; then, we studied the inhibitory effects of ZnCl2, NAC, and KN93 on Cd2+-induced abnormal cell membrane permeability by scanning electrochemical microscopy (SECM) scanning imaging, transverse scanning curve and DPV technology. Our results showed that 10 μmol·L−1 ZnCl2, 0.5 mmol·L−1 NAC and 5 μmol·L−1 KN93 could significantly improve the activity of MCF-7 cells, while did not destroy the cell morphology and membrane permeability. 0.5 mmol·L−1 NAC and 5 μmol·L−1 KN93 could significantly inhibit the effects of Cd2+ on the morphology and membrane permeability of MCF-7 cells (p < 0.01). 10 μmol·L−1 ZnCl2 could significantly inhibit the effect of Cd on the membrane permeability of MCF-7 cells, however, it cannot completely eliminate the morphological changes of MCF-7 cells caused by Cd2+. The results of cell activity experiment showed that 10 μmol·L−1 ZnCl2, 0.5 mmol·L−1 NAC and 5 μmol·L−1 KN93 could inhibit the effect of Cd2+ on the activity of MCF-7 cells. By comparing the inhibitory effects of ZnCl2, NAC and KN93 on Cd2+- induced cytotoxicity, 5 μmol·L−1 KN93 had the robust effect on the maintenance of MCF-7 cell morphology and cell membrane integrity. Our research provided evidence on Zn supplement, NAC as antioxidant drugs, and KN93 as special inhibitor for the detoxification of Cd2+-reduced abnormal cell morphology and membrane permeability.