Effects and Molecular Mechanism of L-Type Calcium Channel on Fluoride-Induced Kidney Injury

  • Dandan Shao
  • Jiayong Zhang
  • Le Tang
  • Qiuli Yu
  • Xiaoxiao Hu
  • Qin Ruan
  • Wei OuyangEmail author
  • Zigui ZhangEmail author


This study aimed to investigate the role and molecular mechanism of L-type calcium channel (LTCC) on fluoride exposure-induced kidney injury. Subchronic and chronic fluoride exposures were included in the experiment. Each part contained 140 ICR male mice. They were randomly divided into 7 groups: control group, high-fluoride group (NaF 30 mg/L), low-fluoride group (NaF 5 mg/L), high/low-fluoride + agonist (FPL64176) group, high/low-fluoride + inhibitor (nifedipine) group. One week before the end of fluoride exposure, each mouse in the fluoride exposure group was injected intraperitoneally with LTCC agonist (FPL64176) or inhibitor (nifedipine) (5 mg/kg day). The apoptosis of kidney cell was observed by TUNEL, and the protein expression levels of Cav1.2 and CaM, CaMKII, Bcl-2, and Bax were detected by Western blot. Compared with the control group, the protein expression levels of Cav1.2, CaM, and Bax significantly increased, and those of CaMKII and Bcl-2 significantly decreased, the ratio of Bax/Bcl-2 also significantly increased, and the number of apoptotic kidney cells significantly increased in the high/low-fluoride group and in the high/low-fluoride + agonist group. The above indicators and fluoride exposure concentrations showed in time- and dose-dependent changes. Compared with the high/low-fluoride + agonist group, the protein expression level of the molecular in the kidney cells above mentioned was significantly opposite and the number of apoptotic kidney cells significantly decreased in the high/low-fluoride + inhibitor group. In conclusion, LTCC mediates the kidney injury induced by fluoride exposure in mice. Fluoride exposure induced abnormal expression of the Cav1.2 protein, Ca2+ signal transduction pathway, and apoptosis-regulated proteins, which is one of the molecular mechanisms. Nifedipine may be a new and effective anti-fluoride drug.


Fluorosis Kidney L-type calcium channel Apoptosis Cav1.2 


Funding Information

This research was sponsored by the National Natural Science Foundation of China (grant number: 81573101).


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.College of Chemistry and Life ScienceZhejiang Normal UniversityZhejiangPeople’s Republic of China
  2. 2.College of Xing ZhiZhejiang Normal UniversityZhejiangPeople’s Republic of China
  3. 3.College of Sports and Health ScienceZhejiang Normal UniversityZhejiangPeople’s Republic of China

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