In Vitro Evaluation of the Apoptotic, Autophagic, and Necrotic Molecular Pathways of Fluoride
1Biochemistry Department, Faculty of Veterinary Medicine, Van Yuzuncu Yil University, 65090, Van, Turkey.
Abstract:
Prolonged exposure to high doses of fluoride causes chronic poisoning called fluorosis, which affects many tissues and causes serious health problems. This study was planned to investigate the apoptotic, autophagic, and necrotic molecular pathways of fluoride. Sodium fluoride (NaF) was administered to normal rat kidney epithelial (NRK-52E) cells. The NaF IC50 value was determined using the MTT assay. The expression of the genes in the autophagic, apoptotic, and necrotic pathways was determined by real-time PCR. It was determined that there were significant changes in NaF-induced molecular pathways depending on the time. There were no increases in apoptotic and necrotic pathway markers except for Atg3, an autophagy gene, at the 3rd and the 12th hours. However, there was an induction in all cell death signaling pathways at 24 h. The molecular mechanisms demonstrated NaF-induced cellular death in the NRK-52E cell line. It was concluded that these molecular mechanisms were activated with NaF, and different mechanisms accelerated the cellular death at the 24th hour.
Insights
High fluoride exposure causes fluorosis. This study found that sodium fluoride (NaF) induced cell death pathways in kidney cells, with all pathways activated after 24 hours.
Area of Science:
- Cell Biology
- Toxicology
- Molecular Biology
Background:
- Fluoride exposure can lead to chronic poisoning, known as fluorosis, impacting multiple tissues and causing severe health issues.
- Understanding the molecular mechanisms of fluoride toxicity is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the apoptotic, autophagic, and necrotic molecular pathways affected by fluoride exposure.
- To determine the time-dependent effects of sodium fluoride (NaF) on these cell death pathways in kidney cells.
Main Methods:
- Sodium fluoride (NaF) was administered to normal rat kidney epithelial (NRK-52E) cells.
- The MTT assay was used to determine the NaF IC50 value.
- Real-time PCR was employed to analyze the expression of genes involved in autophagic, apoptotic, and necrotic pathways.
Main Results:
- NaF exposure induced significant changes in molecular pathways over time.
- Apoptotic and necrotic markers showed no significant increase until 24 hours, except for the autophagy gene Atg3 at 3 and 12 hours.
- All investigated cell death signaling pathways were induced by NaF at the 24-hour time point.
Conclusions:
- NaF induces cellular death in NRK-52E cells through molecular mechanisms involving apoptosis, autophagy, and necrosis.
- These molecular pathways are activated by NaF, with distinct mechanisms accelerating cell death by 24 hours.
