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

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)238-249
Number of pages12
JournalNeurochemical Research
Volume48
Issue number1
DOIs
StatePublished - Jan 2023

Keywords

  • BDNF
  • Lead
  • Neuroinflammation
  • PAS-Na
  • SIRT1/HMGB1/NF-κB pathway

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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