Fluoride effects on cell viability and ENaC expression in kidney epithelial cells
Mariana R Santesso1, Flávia A Oliveira1,2, Cintia K Tokuhara1
1Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, São Paulo, Bauru, Brazil.
Toxicology Mechanisms and Methods
|June 21, 2021
Summary
Fluoride exposure at micromolar concentrations harms kidney cells and alters epithelial sodium channel (ENaC) gene expression. This fluoride-induced modulation of ENaC impacts kidney function and cellular signaling.
Area of Science:
- Nephrology
- Cell Biology
- Toxicology
Background:
- Fluoride (F) at micromolar concentrations induces apoptosis and alters protein expression in various cell types.
- Epithelial sodium channels (ENaCs) are crucial for renal ion transport, electrolyte balance, and homeostasis.
- Understanding fluoride's impact on renal cells and ENaC is vital for kidney health.
Purpose of the Study:
- To investigate the effects of varying sodium fluoride (NaF) concentrations on renal epithelial cell viability.
- To examine the impact of NaF on the expression of epithelial sodium channel (ENaC) subunit genes in M-1 cells.
- To elucidate the role of fluoride in modulating kidney ion transport mechanisms.
Main Methods:
- Renal epithelial cells (M-1) were exposed to different NaF concentrations (10–400 µM).
- Cell viability was assessed over 96 hours.
- ENaC subunit gene expression (Scnn1a, Scnn1b, Scnn1g) was analyzed using quantitative methods and immunofluorescence.
Main Results:
- NaF reduced M-1 cell viability in a concentration-dependent manner.
- Moderate NaF concentrations (100–200 µM) upregulated Scnn1a and Scnn1g, while 400 µM downregulated all ENaC subunit genes.
- Immunofluorescence revealed decreased Scnn1a and Scnn1g expression within 24 hours, with complex temporal changes observed thereafter.
Conclusions:
- Micromolar fluoride concentrations negatively affect renal epithelial cell viability.
- Fluoride exposure modulates the expression of ENaC subunit genes in a concentration- and time-dependent manner.
- These findings suggest fluoride significantly impacts molecular signaling pathways in kidney cells, potentially affecting ion transport.
