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Sodium Para-aminosalicylic Acid Inhibits Lead-Induced Neuroinflammation in Brain Cortex of Rats by Modulating SIRT1/HMGB1/NF-κB Pathway

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Abstract

Lead (Pb) is considered to be a major environmental pollutant and occupational health hazard worldwide which may lead to neuroinflammation. However, an effective treatment for Pb-induced neuroinflammation remains elusive. The aim of this study was to investigate the mechanisms of Pb-induced neuroinflammation, and the therapeutic effect of sodium para-aminosalicylic acid (PAS-Na, a non-steroidal anti-inflammatory drug) in rat cerebral cortex. The results indicated that Pb exposure induced pathological damage in cerebral cortex, accompanied by increased levels of inflammatory factors tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). Moreover, Pb decreased the expression of silencing information regulator 2 related enzyme 1 (SIRT1) and brain-derived neurotrophic factor (BDNF), and increased the levels of high mobile group box 1 (HMGB1) expression and p65 nuclear factor-κB (NF-κB) phosphorylation. PAS-Na treatment ameliorated Pb-induced histopathological changes in rat cerebral cortex. Moreover, PAS-Na reduced the Pb-induced increase of TNF-α and IL-1β levels concomitant with a significant increase in SIRT1 and BDNF levels, and a decrease in HMGB1 and the phosphorylation of p65 NF-κB expression. Thus, PAS-Na may exert anti-inflammatory effects by mediating the SIRT1/HMGB1/NF-κB pathway and BDNF expression. In conclusion, in this novel study PAS-Na was shown to possess an anti-inflammatory effect on cortical neuroinflammation, establishing its efficacy as a potential treatment for Pb exposures.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgements

The authors thank Dr. Yan Li from Guangxi Zhuang Autonomous Region Institute for the Prevention and Treatment of Occupational Disease for her help in the detection of cerebral cortex Pb levels.

Funding

Funding support was provided by grants from the National Natural Science Foundation of China (Grant No. NSFC 81773476).

Author information

Author notes

  1. Yue-song Zhao, Jun-yan Li, and Zhao-cong Li contributed equally to this article.

Authors and Affiliations

  1. Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd., Nanning, 530021, Guangxi, China

    Yue-song Zhao, Jun-yan Li, Zhao-cong Li, Lei-lei Wang, Cui-liu Gan, Jing Chen, Si-yang Jiang, Shi-yan Ou & Yue-ming Jiang

  2. Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China

    Yue-song Zhao, Zhao-cong Li, Lei-lei Wang, Cui-liu Gan, Jing Chen, Si-yang Jiang, Shi-yan Ou & Yue-ming Jiang

  3. Hengyang Center for Disease Control and Prevention, Hengyang, China

    Jun-yan Li

  4. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA

    Michael Aschner

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Contributions

YSZ: Investigation, Formal analysis, Writing original draft, Writing—review & editing. JYL: Investigation, Methodology, Formal analysis, Data curation. ZCL: Investigation, Writing original draft, Writing—review & editing. LLW: Methodology, Formal analysis. CLG, JC and SYJ: Methodology, Validation. MA: Language polishing. SYO: Investigation, Supervision. YMJ: Supervision, Project administration, Funding acquisition.

Corresponding authors

Correspondence to Shi-yan Ou or Yue-ming Jiang.

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All animal procedures performed in this study were performed strictly according to the international standards of animal care guidelines and have been approved by the Animal Care and Use Committee of Guangxi Medical University (Approval Number: 201806386).

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Zhao, Ys., Li, Jy., Li, Zc. et al. Sodium Para-aminosalicylic Acid Inhibits Lead-Induced Neuroinflammation in Brain Cortex of Rats by Modulating SIRT1/HMGB1/NF-κB Pathway. Neurochem Res 48, 238–249 (2023). https://doi.org/10.1007/s11064-022-03739-1

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