An Antagonism Joint Action of Lead and Di-2-Ethylhexyl Phthalate Explains an Improved Ability of Learning and Memory after Combined Exposure in Weaning Rats

  • Liuli Li
  • Hao Li
  • Peng Qu
  • Mingyang Xiao
  • Guopei Zhang
  • Qianye Zhang
  • Yuan Cai
  • Cuihong Jin
  • Jinghua Yang
  • Shengwen Wu
  • Xiaobo LuEmail author


Lead and di-2-ethylhexyl phthalate (DEHP) are widely distributed in the environment, and their neurotoxicity has caused a widespread concern. The complexity of environmental exposure provides the possibility of their combined exposure. The present study aims to describe a joint neurotoxicity and clarify the potential mechanism after combined exposure to lead and DEHP. A 2 × 3 factorial design was used to analyze either single effects or their interaction by a subchronic lead and DEHP exposure model of the male weaning rats. Similar to the previous study, lead or DEHP single exposure showed an increased neurotoxicity. Interestingly, our neurobehavioral test showed the rats in the combined exposure groups had a better ability of learning and memory compared with the single-exposure ones. It seemed to reflect an antagonism joint action in neurotoxicity after combined exposure. The content of dehydroepiandrosterone (DHEA) in serum and the mRNA level of brain-derived neurotrophic factor (Bdnf) in the hippocampus showed a similar trend to the ability of learning and memory. However, there was insufficient evidence to support the joint action on some indexes of oxidative stress such as malondialdehyde (MDA), the ratio of reduced glutathione(GSH) to oxidized glutathione(GSSG), γglutamylcysteine synthetase (γ-GCS), glutathione-s transferase (GST), and nuclear factor E2-related factor 2 (Nrf2) mRNA expression in the hippocampus. In a word, our current study reminded a unique antagonism joint action of neurotoxicity after combined exposure to lead and DEHP, which may contribute to understanding some shallow mechanism of the joint toxicity due to the complexity of environmental pollutant exposure.


Lead DEHP Combined exposure Learning and memory 


Funding Information

This study was supported by the National Natural Science Foundation of China 81773470 and the Provincial Natural Science Foundation of Liaoning 20170540991.

Compliance with Ethical Standards

Ethical approval for all animals involved in this study was from the Institutional Animal Care and Use Committee of China Medical University.

Conflict of Interest

The authors declare that there are no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Liuli Li
    • 1
  • Hao Li
    • 1
  • Peng Qu
    • 1
  • Mingyang Xiao
    • 1
  • Guopei Zhang
    • 1
  • Qianye Zhang
    • 1
  • Yuan Cai
    • 1
  • Cuihong Jin
    • 1
  • Jinghua Yang
    • 1
  • Shengwen Wu
    • 1
  • Xiaobo Lu
    • 1
    Email author
  1. 1.Department of Toxicology, School of Public HealthChina Medical UniversityShenyangPeople’s Republic of China

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