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

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.

• Authors: Jie Wu, Ming Cheng, Qiufang Liu, Jinghua Yang, Shengwen Wu, Xiaobo Lu, Cuihong Jin, Honglin Ma, Yuan Cai
• Journal: Cellular and molecular neurobiology (Cell Mol Neurobiol) Vol. 35 Issue 7 Pg. 1017-25 (Oct 2015) ISSN: 1573-6830 [Electronic] United States
• PMID: 25911493 (Publication Type: Journal Article)

Chemical References

• Hydroquinones
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Reactive Oxygen Species
• Sodium Fluoride
• 2-tert-butylhydroquinone

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Cell Survival (drug effects, physiology)
• Dose-Response Relationship, Drug
• Hydroquinones (pharmacology)
• NF-E2-Related Factor 2 (metabolism)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects, physiology)
• PC12 Cells
• Rats
• Reactive Oxygen Species (metabolism)
• Sodium Fluoride (toxicity)