Genistein alleviates lead-induced neurotoxicity in vitro and in vivo: Involvement of multiple signaling pathways

Peng Su, Jianbin Zhang, Siwang Wang, Michael Aschner, Zipeng Cao, Fang Zhao, Diya Wang, Jiangyuan Chen, Wenjing Luo

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Lead (Pb) is a ubiquitous environmental and industrial pollutant. It induces neurotoxicity and cell death by disrupting the pro- and anti-oxidative balance; however, the mechanisms of its toxicity have yet to be fully understood. The soy-derived isoflavonoid, genistein (GEN), was reported to possess neuroprotective and antioxidative properties. The present study investigated the molecular mechanisms of Pb-induced neurotoxicity in vivo and in vitro, addressing the efficacy of GEN in protecting against Pb-induced toxicity. Pb exposure was associated with reduction of cell viability and cell apoptosis, concomitant with reactive oxygen species (ROS) generation in vitro, and pre-treatment with GEN markedly ameliorated the Pb-induced oxidative injury by increasing the expression of key antioxidant enzymes and the antioxidant transcription factor, nuclear factor erythroid 2 p45-related factor 2 (Nrf2). Next, PKC-α activation was found after Pb exposure in vitro and pretreatment with GEN attenuated Pb-induced ROS generation by PKC-α inhibition. MAPK-NF-κB activation triggered by Pb was also inhibited by GEN. In summary, our study establishes that GEN alleviates Pb-induced impairment in spatial memory, and reduces cell apoptosis caused by Pb exposure and GEN protects neurons from Pb-induced neurotoxicity by downstream activation of antioxidant and anti-apoptotic pathways via regulation of Nrf2 and MAPK-NF-κB signaling.

Original languageEnglish (US)
Pages (from-to)153-164
Number of pages12
JournalNeuroToxicology
Volume53
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Keywords

  • Apoptosis
  • Genistein
  • Lead
  • MAPKs
  • NF-κB
  • Nrf2
  • Oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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