Fluoride effects on cell viability and ENaC expression in kidney epithelial cells

Author(s)

Santesso, Mariana R. ^[1] ; Oliveira, Flavia A. ^{[1, 2]} ; Tokuhara, Cintia K. ^[1] ; Oliveira, Gabriela S. N. ^[1] ; Levy, Flavia M. ^[1] ; Antonio, Ligia S. ^[2] ; Buzalaf, Marilia A. R. ^[1] ; Oliveira, Rodrigo C. ^[1]

Affiliation

^[1] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci, Alameda Dr Octavio Pinheiro Brisolla 975, BR-17012901 Bauru, SP - Brazil

^[2] Univ Cambridge, Dept Pharmacol, Cambridge - England

• Document type: Journal article
• Source: TOXICOLOGY MECHANISMS AND METHODS; v. 31, n. 8, p. 566-571, OCT 13 2021.
• Web of Science Citations: 0

Abstract

Fluoride (F) at micromolar (mu M) concentrations induces apoptosis in several cell lines. Moreover, proteomic studies have shown major changes in the profile of proteins involved in signal transduction. These effects may negatively affect ion transport in the kidneys. The activity of epithelial sodium channels (ENaCs) is a limiting factor for sodium and water resorption in the kidneys, which is essential for the maintenance of the electrolyte balance and homeostasis of the body. Here we investigated the effects of F, at different concentrations (10, 40, 100, 200, and 400 mu M), on the viability of renal epithelial cells (M-1), and ENaC expression. We showed that sodium fluoride (NaF) reduces cell viability in a concentration-dependent manner (p < 0.05) up to a 96-h time-point when compared to control. Sodium fluoride at moderate concentrations (100 and 200 mu M), upregulated the ENaC subunit genes Scnn1a and Scnn1g, but not Scnn1b. Sodium fluoride downregulated all three ENaC subunit genes at a higher concentration of 400 mu M (p < 0.05). Immunofluorescence analysis showed that Scnn1a and Scnn1g expression was decreased within 24 h of NaF treatment. After 48 h, NaF (400 mu M) increased the expression of Scnn1a but not Scnn1g. However, NaF decreased the expression of Scnn1g at all studied concentrations. We conclude that F, at mu M concentrations, modulates the expression of ENaC subunit genes, which is likely to significantly affect molecular signaling in kidney epithelial cells. (AU)

• FAPESP's process: 14/05234-2 - Study of the aqueous extract of leaves of Qualea grandiflora: phytochemical evaluation and effects on the expression of proteins involved in inflammatory processes
• Grantee: Rodrigo Cardoso de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/08890-3 - Study of B4 leukotriene involvement in controlling angiogenesis process osteogenesis coupled to the arthritic condition.
• Grantee: Rodrigo Cardoso de Oliveira
• Support Opportunities: Regular Research Grants