Molecular Neurobiology

, Volume 52, Issue 3, pp 1504–1520 | Cite as

Lead Intoxication Synergies of the Ethanol-Induced Toxic Responses in Neuronal Cells—PC12

  • V. Kumar
  • V. K. Tripathi
  • S. Jahan
  • M. Agrawal
  • A. Pandey
  • V. K. Khanna
  • A. B. Pant
Article

Abstract

Lead (Pb)-induced neurodegeneration and its link with widespread neurobehavioral changes are well documented. Experimental evidences suggest that ethanol could enhance the absorption of metals in the body, and alcohol consumption may increase the susceptibility to metal intoxication in the brain. However, the underlying mechanism of ethanol action in affecting metal toxicity in brain cells is poorly understood. Thus, an attempt was made to investigate the modulatory effect of ethanol on Pb intoxication in PC12 cells, a rat pheochromocytoma. Cells were co-exposed to biological safe doses of Pb (10 μM) and ethanol (200 mM), and data were compared to the response of cells which received independent exposure to these chemicals at similar doses. Ethanol (200 mM) exposure significantly aggravated the Pb-induced alterations in the end points associated with oxidative stress and apoptosis. The finding confirms the involvement of reactive oxygen species (ROS)-mediated oxidative stress, and impairment of mitochondrial membrane potential, which subsequently facilitate the translocation of triggering proteins between cytoplasm and mitochondria. We further confirmed the apoptotic changes due to induction of mitochondria-mediated caspase cascade. These cellular changes were found to recover significantly, if the cells are exposed to N-acetyl cysteine (NAC), a known antioxidant. Our data suggest that ethanol may potentiate Pb-induced cellular damage in brain cells, but such damaging effects could be recovered by inhibition of ROS generation. These results open up further possibilities for the design of new therapeutics based on antioxidants to prevent neurodegeneration and associated health problems.

Keywords

Neurotoxicity Pb Ethanol PC12 cells 

Notes

Acknowledgments

The authors are grateful to the Director, IITR, Lucknow, India, for his keen interest in the study. Financial support from Department of Biotechnology, Ministry of Science & Technology, Government of India, New Delhi, India [Grant No. 102/IFD/SAN/PR1524/2010–2011]; Department of Science and Technology, Ministry of Science & Technology, Government of India, New Delhi, India [Grant No. SR/SO/Z 36/2007/91/10]; and Council of Scientific & Industrial Research, Government of India, New Delhi, India [Grant No. BSC0111/INDEPTH/ CSIR Network Project] is acknowledged. Indian Council of Medical Research, (ICMR), New Delhi, India, is acknowledged for providing the fellowship to Dr. Vivek Kumar. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article.

Conflict of Interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • V. Kumar
    • 1
    • 2
  • V. K. Tripathi
    • 1
    • 2
  • S. Jahan
    • 1
    • 2
  • M. Agrawal
    • 1
    • 2
  • A. Pandey
    • 1
    • 2
  • V. K. Khanna
    • 1
    • 2
  • A. B. Pant
    • 1
    • 2
  1. 1.In Vitro Toxicology LaboratoryIndian Institute of Toxicology ResearchLucknowIndia
  2. 2.Council of Scientific & Industrial ResearchNew DelhiIndia

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