Sodium fluoride induces apoptosis in mouse splenocytes by activating ROS-dependent NF-κB signaling

Huidan Deng1, Ping Kuang1, Hengmin Cui1,2

  • 1College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China.

Oncotarget
|February 1, 2018
PubMed

Insights

Sodium fluoride exposure causes DNA damage and cell death in mouse immune cells. This occurs through increased reactive oxygen species (ROS) and nuclear factor-kappa B (NF-κB) signaling pathways.

Area of Science:

  • Immunotoxicology
  • Cellular and Molecular Toxicology

Background:

  • Sodium fluoride (NaF) is an environmental contaminant with known toxic effects.
  • The mechanisms underlying NaF-induced cellular damage, particularly in immune cells, require further elucidation.

Purpose of the Study:

  • To investigate the roles of reactive oxygen species (ROS) and nuclear factor-kappa B (NF-κB) signaling in sodium fluoride-induced DNA damage and apoptosis in mouse splenocytes.

Main Methods:

  • Mice were administered varying doses of sodium fluoride (12, 24, or 48 mg/kg) via intragastric gavage.
  • Splenocytes were analyzed for DNA fragmentation, apoptosis, ROS levels, and expression of key proteins in the NF-κB pathway and apoptosis-related proteins at 21 and 42 days post-treatment.

Main Results:

  • Sodium fluoride exposure led to a time- and dose-dependent increase in DNA fragmentation and apoptosis in mouse splenocytes.
  • Elevated ROS levels were observed, correlating with increased phosphorylated IκB kinase and NF-κB p65, and decreased inhibitory kappa B protein.
  • NaF-treated splenocytes exhibited increased expression of pro-apoptotic proteins (Bim, Bax, Bak, caspase-3, PARP) and decreased expression of anti-apoptotic proteins (Bcl-2, Bcl-xL).

Conclusions:

  • Sodium fluoride induces apoptosis in mouse splenocytes.
  • This apoptosis is mediated by enhanced ROS production and subsequent activation of the NF-κB signaling pathway.

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