Divergent Effects of Arsenic on NF-κB Signaling in Different Cells or Tissues: A Systematic Review and Meta-Analysis.

Meng Wei,Gangling Feng,Shuxia Guo,Shugang Li,Mengchuan Xu,Jiaming Liu,Dongsheng Rui,Shangzhi Xu,Yusong Ding

doi:10.3390/ijerph13020163

Meng Wei, Gangling Feng + Show 7 more

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https://doi.org/10.3390/ijerph13020163

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Abstract

Arsenic is ubiquitously present in human lives, including in the environment and organisms, and has divergent effects between different cells and tissues and between different exposure times and doses. These observed effects have been attributed to the nuclear transcription factor kappa B(NF-κB) signaling pathway. Herein, a meta-analysis was performed by independently searching databases including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze effects of arsenic exposure on NF-κB signaling. Compared to controls, in the exposed group, p-IκB levels were found to be 8.13-fold higher (95% CI, 2.40–13.85; Z = 2.78; p = 0.005), IκB levels were 16.19-fold lower (95% CI, −27.44–−4.94; Z = 2.78; p = 0.005), and NF-κBp65 levels were 0.77-fold higher (95% CI, 0.13–1.42; Z = 2.34; p = 0.02) for normal cells and tissue, while NF-κBp65 levels were 4.90-fold lower (95% CI, −8.49–1.31; Z = 2.62; p = 0.009), NF-κB activity was 2.45-fold lower (95% CI, −3.66–1.25; Z = 4.00; p < 0.0001), and DNA-binding activity of NF-κB was 9.75-fold lower (95% CI, −18.66–4.54; Z = 2.15; p = 0.03) for abnormal cells and tissue. Short exposure to high arsenic doses activated the NF-κB signaling pathway, while long exposure to low arsenic doses suppressed NF-κB signaling pathway activation. These findings may provide a theoretical basis for injurious and therapeutic mechanisms of divergent effects of arsenic.

Highlights

Arsenic exists ubiquitously on earth including in the earth’s crust, in soil, in water, in air, in food, and in organisms [1,2]
The analysis demonstrated that arsenic exposure times of ď24 h promote phosphorylation of IκB (p = 0.0002), induce weak NF-κB activity exposure times of ≤24 h promote phosphorylation of IκB (p = 0.0002), induce weak NF‐κB activity (p = 0.02), and increase NF-κBp65 expression (p = 0.04), while arsenic exposure times ą24 h suppresses (p = 0.02), and increase NF‐κBp65 expression (p = 0.04), while arsenic exposure times24 h
The findings of this meta‐analysis reveal that arsenic activates the NF‐κB signaling pathway in Thecells findings of this meta‐analysis that arsenic activates the NF‐κBeffects signaling pathwayare in normal or tissues; thereveal antitumor and anti‐inflammatory of arsenic normal cells or tissues; the antitumor and anti‐inflammatory effects of arsenic are. The findings of this meta-analysis reveal that arsenic activates the NF-κB signaling pathway in normal cells or tissues; the antitumor and anti-inflammatory effects of arsenic are accompanied by partial suppression of the NF-κB signaling pathway

Summary

Introduction

Arsenic exists ubiquitously on earth including in the earth’s crust, in soil, in water, in air, in food, and in organisms [1,2]. 200 million people worldwide are threatened by arsenic poisoning, and the number of people suffering from arsenic poisoning due to water contamination alone is more than 3 million in China [3]. Epidemic investigations and studies have shown that inorganic arsenic may increase the risk of many cancers including bladder, kidney, liver, lung, prostate, and skin cancer [4,5,6,7,8]. The risks of other diseases including cardiovascular disease [9], hypertension [10], and diabetes [11] are increased by arsenic. Investigations into arsenic poison effects and related molecular mechanisms as well as those of the therapeutic effects of arsenic have

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