Therapeutic Effects of Sodium Para-Aminosalicylic Acid on Cognitive Deficits and Activated ERK1/2-p90RSK/NF-κB Inflammatory Pathway in Pb-Exposed Rats

Li li Lu, Yu wen Zhang, Zhao cong Li, Yuan yuan Fang, Lei lei Wang, Yue song Zhao, Shao jun Li, Shi yan Ou, Michael Aschner, Yue ming Jiang

Research output: Contribution to journalArticlepeer-review

Abstract

Lead (Pb) is a toxic heavy metal and environmental pollutant that adversely affects the nervous system. However, effective therapeutic drugs for Pb-induced neurotoxicity have yet to be developed. In the present study, we investigated the ameliorative effect of sodium para-aminosalicylic acid (PAS-Na) on Pb-induced neurotoxicity. Male Sprague–Dawley rats were treated with (CH3COO)2 Pb•4H2O (6 mg/kg) for 4 weeks, followed by 3 weeks of PAS-Na (100, 200, and 300 mg/kg). The results showed that subacute Pb exposure significantly decreased rats body-weight gains and increased liver coefficient, and impaired spatial learning and memory. HE staining showed that Pb damaged the structure of the hippocampus. Moreover, Pb activated the ERK1/2-p90RSK/ NF-κB pathway concomitant with increased inflammatory cytokine IL-1β levels in rat hippocampus. PAS-Na reversed the Pb-induced increase in the liver coefficient as well as the learning and memory deficits. In addition, PAS-Na reduced the phosphorylation of ERK1/2, p90RSK and NF-κB p65, decreasing IL-1β levels in hippocampus. Our findings indicated that PAS-Na showed efficacy in reversing Pb-induced rats cognitive deficits and triggered an anti-inflammatory response. Thus, PAS-Na may be a promising therapy for treating Pb-induced neurotoxicity.

Original languageEnglish (US)
JournalBiological Trace Element Research
DOIs
StateAccepted/In press - 2021

Keywords

  • Inflammatory pathway
  • Lead exposure
  • Learning and memory deficits
  • PAS-Na
  • Rats

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry
  • Inorganic Chemistry
  • Biochemistry, medical

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