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Rotenone-induced oxidative stress and apoptosis in human liver HepG2 cells

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Abstract

Rotenone, a commonly used pesticide, is well documented to induce selective degeneration in dopaminergic neurons and motor dysfunction. Such rotenone-induced neurodegenration has been primarily suggested through mitochondria-mediated apoptosis and reactive oxygen species (ROS) generation. But the status of rotenone induced changes in liver, the major metabolic site is poorly investigated. Thus, the present investigation was aimed to study the oxidative stress-induced cytotoxicity and apoptotic cell death in human liver cells-HepG2 receiving experimental exposure of rotenone (12.5–250 μM) for 24 h. Rotenone depicted a dose-dependent cytotoxic response in HepG2 cells. These cytotoxic responses were in concurrence with the markers associated with oxidative stress such as an increase in ROS generation and lipid peroxidation as well as a decrease in the glutathione, catalase, and superoxide dismutase levels. The decrease in mitochondrial membrane potential also confirms the impaired mitochondrial activity. The events of cytotoxicity and oxidative stress were found to be associated with up-regulation in the expressions (mRNA and protein) of pro-apoptotic markers viz., p53, Bax, and caspase-3, and down-regulation of anti-apoptotic marker Bcl-2. The data obtain in this study indicate that rotenone-induced cytotoxicity in HepG2 cells via ROS-induced oxidative stress and mitochondria-mediated apoptosis involving p53, Bax/Bcl-2, and caspase-3.

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Acknowledgments

Financial support from National Plan for Sciences and Technology (NPST Project No. 10-ENV1314-02) and DNA Research Chair, King Saud University, Riyadh is acknowledged.

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Authors and Affiliations

  1. Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    M. A. Siddiqui, J. Ahmad, Q. Saquib, J. Musarrat & A. A. Al-Khedhairy

  2. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

    N. N. Farshori

  3. In Vitro Toxicology Laboratory, CSIR-Indian Institute of Toxicology Research, Lucknow, India

    S. Jahan & M. P. Kashyap

  4. King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia

    M. Ahamed

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  1. M. A. Siddiqui
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Correspondence to M. A. Siddiqui.

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Siddiqui, M.A., Ahmad, J., Farshori, N.N. et al. Rotenone-induced oxidative stress and apoptosis in human liver HepG2 cells. Mol Cell Biochem 384, 59–69 (2013). https://doi.org/10.1007/s11010-013-1781-9

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