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

Huidan Deng,Yujiao Lu,Huan Liu,Ping Kuang,Junliang Deng,Yinglun Li,Ling Zhao,Hengmin Cui,Zhicai Zuo,Qin Luo,Xun Wang,Jing Fang

doi:10.18632/oncotarget.22826

Huidan Deng, Yujiao Lu + Show 10 more

Open Access

https://doi.org/10.18632/oncotarget.22826

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Abstract

In this study, we investigated the roles of reactive oxygen species (ROS) and nuclear factor-κB (NF-κB) signaling in sodium fluoride-induced DNA damage and apoptosis in mouse splenocytes. Intragastric administration of 12, 24 or 48 mg/kg sodium fluoride resulted in a time- and dose-dependent increase in DNA fragmentation and apoptosis in mouse splenocytes on days 21 and 42. High ROS levels correlated with increased levels of phosphorylated IκB kinase and NF-κB p65 and decreased levels of inhibitory kappa B protein in splenocytes from mice treated with sodium fluoride. Moreover, splenocytes from sodium fluoride-treated mice showed high expression of pro-apoptotic proteins, including Bim, Bax, Bak, caspase-3 and poly ADP-ribose polymerase, and low expression of the anti-apoptotic proteins BcL-2 and BcL-xL. These results show that sodium fluoride induces apoptosis in mouse splenocytes by enhancing ROS-dependent NF-κB signaling.

Highlights

Prolonged intake of fluoridated drinking water and food results in dental, skeletal and non-skeletal fluorosis [1, 2]
We investigated the roles of reactive oxygen species (ROS) and nuclear factor-κB (NF-κB) signaling in sodium fluoride-induced DNA damage and apoptosis in mouse splenocytes
Splenocytes from sodium fluoride-treated mice showed high expression of pro-apoptotic proteins, including Bim, Bax, Bak, caspase-3 and poly ADP-ribose polymerase, and low expression of the anti-apoptotic proteins BcL-2 and BcL-xL. These results show that sodium fluoride induces apoptosis in mouse splenocytes by enhancing ROS-dependent NF-κB signaling

Summary

Introduction

Prolonged intake of fluoridated drinking water and food results in dental, skeletal and non-skeletal fluorosis [1, 2]. Non-skeletal fluorosis is characterized by severe gastrointestinal, neurological, muscular and hematological symptoms in both humans and animals [3,4,5,6,7]. High dietary fluoride affects humoral and cellular immunity by decreasing levels of serum cytokines and immunoglobulins [8, 9]. High ROS levels induce changes in cellular structure and function as a result of somatic DNA mutations that eventually promote neoplastic transformation [12, 13]. Sodium fluoride alters transcription of xenobiotic metabolizing enzymes in zebra fish by increasing ROS [14]. Fluoride increase the level of ROS contributing to cytotoxicity in human neuroblastoma SH-SY5Y cells [15]

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