Sodium P-aminosalicylic acid inhibits sub-chronic manganese-induced neuroinflammation in rats by modulating MAPK and COX-2

Shao Jun Li, Wen Xia Qin, Dong Jie Peng, Zong Xiang Yuan, Sheng Nan He, Yi Ni Luo, Michael Aschner, Yue Ming Jiang, Dian Yin Liang, Bing Yan Xie, Fang Xu

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Excessive manganese (Mn) accumulation in the brain may induce an extrapyramidal disorder known as manganism. Inflammatory processes play a critical role in neurodegenerative diseases. Therapeutically, non-steroidal anti-inflammatory drugs or analogous anti-inflammatory therapies have neuroprotective effects. As a non-steroidal anti-inflammatory drug, p-aminosalicylic acid (PAS) has anti-inflammatory effects, which are mediated by decreased prostaglandins E2 (PGE2) levels. The aim of the current study was to investigate whether PAS-Na treatment prevents Mn-induced behavioral changes and neuroinflammation in vivo. Male Sprague-Dawley rats were intraperitoneally (i.p.) injected with MnCl 2 ·4H 2 O (15 mg/kg) for 12 weeks, followed by 6 weeks PAS-Na treatment. Sub-chronic Mn exposure increased Mn levels in the whole blood, cortex, hippocampus and thalamus, and induced learning and memory deficits, concomitant with astrocytes activation in the cortex, hippocampus and thalamus. Moreover inflammatory cytokine levels in serum and brain of Mn-treated group were increased, including IL-1β, IL-6, TNF-αand PGE2, especially in the hippocampus and thalamus. Furthermore, sub-chronic Mn exposure also increased inflammatory cytokines and COX-2 in transcription levels concomitant with increased MAPK signaling and COX-2 in the same selected brain regions. PAS-Na treatment at the highest doses also decreased Mn levels in the whole blood and selected brain tissues, and reversed the Mn-induced learning and memory deficits. PAS-Na inhibited astrocyte activation as well as the Mn-induced increase in inflammatory cytokine levels, reducing p38, ERK MAPK pathway and COX-2 activity. In contrast PAS-Na had no effects on the JNK MAPK pathway. These data establish the efficacy of PAS-Na not only as a chelating agent to mobilize whole blood Mn, but also as an anti-inflammatory agent.

Original languageEnglish (US)
Pages (from-to)219-229
Number of pages11
JournalNeurotoxicology
Volume64
DOIs
StatePublished - Jan 2018

Keywords

  • Inflammatory process
  • Learning and memory deficits
  • MAPK pathway
  • Manganese
  • Sodium para-aminosalicylate

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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