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

21 Citations (Scopus)

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

Fingerprint

Genistein
Antioxidants
Chemical activation
Toxicity
Reactive Oxygen Species
NF-E2 Transcription Factor
Apoptosis
Environmental Pollutants
Cell death
Lead
In Vitro Techniques
Neurons
Cell Survival
Cell Death
Cells
Data storage equipment
Wounds and Injuries
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Genistein alleviates lead-induced neurotoxicity in vitro and in vivo : Involvement of multiple signaling pathways. / Su, Peng; Zhang, Jianbin; Wang, Siwang; Aschner, Michael; Cao, Zipeng; Zhao, Fang; Wang, Diya; Chen, Jiangyuan; Luo, Wenjing.

In: NeuroToxicology, Vol. 53, 01.03.2016, p. 153-164.

Research output: Contribution to journalArticle

Su, Peng ; Zhang, Jianbin ; Wang, Siwang ; Aschner, Michael ; Cao, Zipeng ; Zhao, Fang ; Wang, Diya ; Chen, Jiangyuan ; Luo, Wenjing. / Genistein alleviates lead-induced neurotoxicity in vitro and in vivo : Involvement of multiple signaling pathways. In: NeuroToxicology. 2016 ; Vol. 53. pp. 153-164.
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