Sodium Fluoride Causes Oxidative Stress and Apoptosis in the Mouse Liver

Aging (Albany NY). 2017 Jun 27;9(6):1623-1639. doi: 10.18632/aging.101257.

Abstract

The current study was conducted to investigate the effect of sodium fluoride (NaF) on the oxidative stress and apoptosis as well as their relationship in the mouse liver by using methods of flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, biochemistry and experimental pathology. 240 four-week-old ICR mice were randomly divided into 4 groups and exposed to different concentration of NaF (0 mg/kg, 12 mg/kg, 24 mg/kg and 48 mg/kg) for a period of 42 days. The results showed that NaF caused oxidative stress and apoptosis. NaF-caused oxidative stress was accompanied by increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreasing mRNA expression levels and activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-PX) and glutathione-s-transferase (GST). NaF induced apoptosis via tumor necrosis factor recpter-1 (TNF-R1) signaling pathway, which was characterized by significantly increasing mRNA and protein expression levels of TNF-R1, Fas associated death domain (FADD), TNFR-associated death domain (TRADD), cysteine aspartate specific protease-8 (caspase-8) and cysteine aspartate specific protease-3 (caspase-3) in dose- and time-dependent manner. Oxidative stress is involved in the process of apoptotic occurrence, and can be triggered by promoting ROS production and reducing antioxidant function. NaF-caused oxidative stress and apoptosis finally impaired hepatic function, which was strongly supported by the histopathological lesions and increased serum alanine amino transferase (ALT), aspartic acid transferase (AST), alkaline phosphatase (AKP) activities and TBIL contents.

Keywords: TNF-R1 signaling pathway; apoptosis; liver; mouse; oxidative stress; sodium fluoride.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apoptosis / drug effects*
  • Cariostatic Agents
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Liver / drug effects*
  • Mice
  • Oxidative Stress / drug effects*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species
  • Receptors, Death Domain / metabolism
  • Sodium Fluoride / administration & dosage
  • Sodium Fluoride / adverse effects*

Substances

  • Antioxidants
  • Cariostatic Agents
  • RNA, Messenger
  • Reactive Oxygen Species
  • Receptors, Death Domain
  • Sodium Fluoride