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Oxidative stress-mediated cytotoxicity of Endosulfan is causally linked to the inhibition of NADH dehydrogenase and Na+, K+-ATPase in Ehrlich ascites tumor cells

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Abstract

Oxidative stress in cells caused by excessive production of reactive oxygen species (ROS) and decreased antioxidant defense is implicated in the cytotoxicity of xenobiotics including drugs and environmental chemicals. Endosulfan, a highly toxic organochlorine insecticide, causes cytotoxic cell death by inducing oxidative stress. We have investigated the biochemical basis of induction of oxidative stress, involving the role of NADH dehydrogenase and the possible role of Na+, K+-ATPase in endosulfan cytotoxicity and, whether the cytotoxicity could be attenuated by targeting ROS induction using the natural flavonoid antioxidant, quercetin, in Ehrlich ascites tumor (EAT) cells. Exposure of cells to endosulfan caused cytotoxic cell death (necrosis) which was associated with induction of ROS, lipid peroxidation as well as a reduction in glutathione levels, concomitant with loss of NADH dehydrogenase and Na+, K+-ATPase activity in a dose-dependent manner, indicating that oxidative stress and perturbation of membrane function are the major causes of endosulfan cytotoxicity. Our results showed that quercetin, protected against endosulfan-induced cytotoxicity and significantly abrogated oxidative stress, and ameliorated the inhibition of NADH dehydrogenase and Na+, K+-ATPase activity in EAT cells. Our study presents evidence that NADH dehydrogenase inhibition plays an important role in oxidative stress-mediated cytotoxicity, and perturbed membrane function as evident from inhibition of sodium–potassium pump is involved in cytotoxic cell death.

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Acknowledgements

This work was carried out as a part of the M.Sc. dissertation of the first two authors at Central Food Technological Research Institute, Mysore, India, during the senior author’s tenure. The authors thank Dr. Anup Srivastava, Dr. Y. Rajashekar and K.R. Ritesh for their technical and timely help. The authors also thank the Director of the institute for supporting this study.

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  1. Megha Murali

    Present address: Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N4N1, Canada

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  1. CSIR-Central Food Technological Research Institute, Mysore, 570020, India

    Megha Murali, Mary Sweeta Carvalho & T. Shivanandappa

  2. Department of Zoology, University of Mysore, Manasagangotri, Mysore, Karnataka, 570006, India

    Megha Murali, Mary Sweeta Carvalho & T. Shivanandappa

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Murali, M., Carvalho, M.S. & Shivanandappa, T. Oxidative stress-mediated cytotoxicity of Endosulfan is causally linked to the inhibition of NADH dehydrogenase and Na+, K+-ATPase in Ehrlich ascites tumor cells. Mol Cell Biochem 468, 59–68 (2020). https://doi.org/10.1007/s11010-020-03711-z

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