Skip to main content

Advertisement

SpringerLink
Log in

Protective Role of tert-Butylhydroquinone Against Sodium Fluoride-Induced Oxidative Stress and Apoptosis in PC12 Cells

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The neurotoxicity of fluoride is associated with oxidative stress due to imbalance between production and removal of reactive oxygen species (ROS). In contrast, induction of detoxifying and antioxidant genes through activation of NF-E2-related factor 2 (Nrf2) has been implicated in preventing oxidative stress and apoptosis in neurodegenerative diseases. The present study aimed to investigate the possible neuroprotective role of tert-butylhydroquinone (tBHQ), a general Nrf2 activator, on sodium fluoride (NaF)-induced oxidation damage and apoptosis in neuron-like rat pheochromocytoma (PC12) cells. Pretreatment with tBHQ protected PC12 cells against NaF-induced cytotoxicity as measured by MTT assay and apoptosis detection, simultaneously, inhibited NaF-induced overproduction of intracellular ROS and reduction of total glutathione content. Furthermore, NaF or tBHQ induced the stabilization of Nrf2, and enhanced expression of heme oxygenase-1 (HO-1) and γ-glutamylcysteine synthetase (γ-GCS) as a consequence of Nrf2 inducing. These findings indicated that tBHQ pretreatment conferred protective effect on PC12 cells against NaF-induced apoptotic cell death and oxidation-redox imbalance through stabilization of Nrf2 and elevation of downstream HO-1 and γ-GCS expressions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Akhter H, Katre A, Li L, Liu X, Liu RM (2011) Therapeutic potential and anti-amyloidosis mechanisms of tert-butylhydroquinone for Alzheimer’s disease. J Alzheimer’s Dis 26:767–778

    Google Scholar 

  • Atmaca N, Atmaca HT, Kanici A et al (2014) Protective effect of resveratrol on sodium fluoride-induced oxidative stress, hepatotoxicity and neurotoxicity in rats. Food Chem Toxicol 70:191–197

    Article  CAS  PubMed  Google Scholar 

  • Barbier O, Arreola-Mendoza L, Del Razo LM (2010) Molecular mechanisms of fluoride toxicity. Chem Biol Interact 188(2):319–333

    Article  CAS  PubMed  Google Scholar 

  • Basha PM, Madhusudhan N (2010) Pre and post natal exposure of fluoride induced oxidative macromolecular alterations in developing central nervous system of rat and amelioration by antioxidants. Neurochem Res 35(7):1017–1028

    Article  CAS  PubMed  Google Scholar 

  • Basha PM, Rai P, Begum S (2011) Evaluation of fluoride-induced oxidative stress in rat brain: a multigeneration study. Biol Trace Elem Res 142(3):623–637

    Article  CAS  PubMed  Google Scholar 

  • Bharti VK, Srivastava RS (2009) Fluoride-induced oxidative stress in rat’s brain and its amelioration by buffalo (Bubalus bubalis) pineal proteins and melatonin. Biol Trace Elem Res 130(2):131–140

    Article  CAS  PubMed  Google Scholar 

  • Calkins MJ, Johnson DA, Townsend JA et al (2009) The Nrf2/ARE pathway as a potential therapeutic target in neurodegenerative disease. Antioxid Redox Signal 11(3):497–508

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Choi AL, Sun G, Zhang Y et al (2012) Developmental fluoride neurotoxicity: a systematic review and meta-analysis. Environ Health Perspect 120(10):1362–1368

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gan L, Johnson JA (2014) Oxidative damage and the Nrf2-ARE pathway in neurodegenerative diseases. Biochim Biophys Acta 1842(8):1208–1218

    Article  CAS  PubMed  Google Scholar 

  • Greene LA, Tischler AS (1976) Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci USA 73:2424–2428

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gui C-Z, Ran L-Y, Li J-P et al (2010) Changes of learning and memory ability and brain nicotinic receptors of rat offspring with coal burning fluorosis. Neurotoxicol Teratol 32(5):536–541

    Article  CAS  PubMed  Google Scholar 

  • Hybertson BM, Gao B (2014) Role of the Nrf2 signaling system in health and disease. Clin Genet 86(5):447–452

    Article  CAS  PubMed  Google Scholar 

  • Jiang GZ, Li JC (2014) Protective effects of ginsenoside Rg1 against colistin sulfate-induced neurotoxicity in PC12 cells. Cell Mol Neurobiol 34:167–172

    Article  CAS  PubMed  Google Scholar 

  • Jiang C, Zhang S, Liu H et al (2013) Low Glucose Utilization and Neurodegenerative Changes Caused by Sodium Fluoride Exposure in Rat’s Developmental Brain. Neuromolecular Med. doi:10.1007/s12017-013-8260-z

    Google Scholar 

  • Jin X, Liu Q, Jia L et al (2014) Pinocembrin Attenuates 6-OHDA-induced Neuronal Cell Death Through Nrf2/ARE Pathway in SH-SY5Y Cells. Cell Mol Neurobiol. doi:10.1007/s10571-014-0128-8

    Google Scholar 

  • Johnson JA, Johnson DA, Kraft AD et al (2008) The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann N Y Acad Sci 1147:61–69

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Joshi G, Johnson JA (2012) The Nrf2-ARE pathway: a valuable therapeutic target for the treatment of neurodegenerative diseases. Recent Pat CNS Drug Discov 7(3):218–229

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jothiramajayam M, Sinha S, Ghosh M et al (2014) Sodium fluoride promotes apoptosis by generation of reactive oxygen species in human lymphocytes. J Toxicol Environ Health A 77(21):1269–1280

    Article  CAS  PubMed  Google Scholar 

  • Khodagholi F, Tusi SK (2011) Stabilization of Nrf2 by tBHQ prevents LPS-induced apoptosis in differentiated PC12 cells. Mol Cell Biochem 354(1–2):97–112

    Article  CAS  PubMed  Google Scholar 

  • Li J, Johnson D, Calkins M et al (2005) Stabilization of Nrf2 by tBHQ confers protection against oxidative stress-induced cell death in human neural stem cells. Toxicol Sci 83(2):313–328

    Article  CAS  PubMed  Google Scholar 

  • Li H, Wu S, Shi N et al (2011) NF-E2-related factor 2 activation in PC12 cells: its protective role in manganese-induced damage. Arch Toxicol 85(8):901–910

    Article  CAS  PubMed  Google Scholar 

  • Li H, Wu S, Wang Z et al (2012) Neuroprotective effects of tert-butylhydroquinone on paraquat-induced dopaminergic cell degeneration in C57BL/6 mice and in PC12 cells. Arch Toxicol 86(11):1729–1740

    Article  CAS  PubMed  Google Scholar 

  • Liu F, Ma J, Zhang H et al (2014) Fluoride exposure during development affects both cognition and emotion in mice. Physiol Behav 124:1–7

    Article  CAS  PubMed  Google Scholar 

  • Lou H, Jing X, Ren D et al (2012) Eriodictyol protects against H(2)O(2)-induced neuron-like PC12 cell death through activation of Nrf2/ARE signaling pathway. Neurochem Int 61(2):251–257

    Article  CAS  PubMed  Google Scholar 

  • Miao K, Zhang L, Yang S et al (2013) Intervention of selenium on apoptosis and Fas/FasL expressions in the liver of fluoride-exposed rats. Environ Toxicol Pharmacol 36(3):913–920

    Article  CAS  PubMed  Google Scholar 

  • Nabavi SF, Nabavi SM, Habtemariam S et al (2013) Neuroprotective effects of methyl-3-O-methyl gallate against sodium fluoride-induced oxidative stress in the brain of rats. Cell Mol Neurobiol 33(2):261–267

    Article  CAS  PubMed  Google Scholar 

  • Nguyen Ngoc TD, Son YO, Lim SS et al (2012) Sodium fluoride induces apoptosis in mouse embryonic stem cells through ROS-dependent and caspase- and JNK-mediated pathways. Toxicol Appl Pharmacol 259(3):329–337

    Article  CAS  PubMed  Google Scholar 

  • Nouhi F, Tusi SK, Abdi A et al (2011) Dietary supplementation with tBHQ, an Nrf2 stabilizer molecule, confers neuroprotection against apoptosis in amyloid beta-injected rat. Neurochem Res 36(5):870–878

    Article  CAS  PubMed  Google Scholar 

  • Pereira M, Dombrowski PA, Losso EM et al (2011) Memory impairment induced by sodium fluoride is associated with changes in brain monoamine levels. Neurotox Res 19(1):55–62

    Article  CAS  PubMed  Google Scholar 

  • Saxena S, Sahay A, Goel P (2012) Effect of fluoride exposure on the intelligence of school children in Madhya Pradesh. India. J Neurosci Rural Pract 3(2):144–149

    Article  PubMed  Google Scholar 

  • Song GH, Gao JP, Wang CF et al (2014) Sodium fluoride induces apoptosis in the kidney of rats through caspase-mediated pathways and DNA damage. J Physiol Biochem 70(3):857–868

    Article  CAS  PubMed  Google Scholar 

  • Thanan R, Oikawa S, Hiraku Y et al (2014) Oxidative Stress and Its Significant Roles in Neurodegenerative Diseases and Cancer. Int J Mol Sci 16(1):193–217

    Article  PubMed Central  PubMed  Google Scholar 

  • Wang Z, Yang X, Yang S et al (2011) Sodium fluoride suppress proliferation and induce apoptosis through decreased insulin-like growth factor-I expression and oxidative stress in primary cultured mouse osteoblasts. Arch Toxicol 85(11):1407–1417

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Cui KP, Xu YY et al (2013) Coal-burning endemic fluorosis is associated with reduced activity in antioxidative enzymes and Cu/Zn-SOD gene expression. Environ Geochem Health. doi:10.1007/s10653-013-9522-2

    Google Scholar 

  • Wu J, Yang J, Liu Q et al (2013) Lanthanum induced primary neuronal apoptosis through mitochondrial dysfunction modulated by Ca(2)(+) and Bcl-2 family. Biol Trace Elem Res 152(1):125–134

    Article  CAS  PubMed  Google Scholar 

  • Xu Z, Xu B, Xia T et al (2013) Relationship between intracellular Ca(2)(+) and ROS during fluoride-induced injury in SH-SY5Y cells. Environ Toxicol 28(6):307–312

    Article  CAS  PubMed  Google Scholar 

  • Zhang M, Wang A, He W et al (2007) Effects of fluoride on the expression of NCAM, oxidative stress, and apoptosis in primary cultured hippocampal neurons. Toxicology 236(3):208–216

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Zhang X, Liu H et al (2015) Modifying effect of COMT gene polymorphism and a predictive role for proteomics analysis in children’s intelligence in endemic fluorosis area in Tianjin, China. Toxicol Sci. doi:10.1093/toxsci/kfu311

    Google Scholar 

Download references

Conflict of interest

The authors declare that there are no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Toxicology, School of Public Health, China Medical University, Shenyang, 110013, Liaoning, China

    Jie Wu, Ming Cheng, Qiufang Liu, Jinghua Yang, Shengwen Wu, Xiaobo Lu, Cuihong Jin & Yuan Cai

  2. Department of Occupational and Environmental Health, School of Public Health, Liaoning Medical University, Jinzhou, 121001, Liaoning, China

    Jie Wu & Honglin Ma

Authors
  1. Jie Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ming Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiufang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jinghua Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shengwen Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaobo Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cuihong Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Honglin Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuan Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuan Cai.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, J., Cheng, M., Liu, Q. et al. Protective Role of tert-Butylhydroquinone Against Sodium Fluoride-Induced Oxidative Stress and Apoptosis in PC12 Cells. Cell Mol Neurobiol 35, 1017–1025 (2015). https://doi.org/10.1007/s10571-015-0196-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-015-0196-4

Keywords

Search

Navigation