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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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Relation http://ir.cftri.com/14277/
https://doi.org/10.1007/s11010-020-03711-z
 
Title Oxidative stress‑mediated cytotoxicity of Endosulfan is causally
linked to the inhibition of NADH dehydrogenase and Na+,
K+
‑ATPase
in Ehrlich ascites tumor cells.
 
Creator Megha, Murali
Mary Sweeta, Carvalho
Shivanandappa, T.
 
Subject 17 Toxicology
 
Description 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.
 
Date 2020
 
Type Article
PeerReviewed
 
Format pdf
 
Language en
 
Identifier http://ir.cftri.com/14277/1/Molecular%20and%20Cellular%20Biochemistry.pdf
Megha, Murali and Mary Sweeta, Carvalho and Shivanandappa, T. (2020) Oxidative stress‑mediated cytotoxicity of Endosulfan is causally linked to the inhibition of NADH dehydrogenase and Na+, K+ ‑ATPase in Ehrlich ascites tumor cells. Molecular and Cellular Biochemistry, 468 (1-2). pp. 59-68.