Causal relationship between hexachlorocyclohexane cytotoxicity, oxidative stress and Na+, K +-ATPase in Ehrlich Ascites tumor cells.
Role of oxidative stress and Na+,K+-ATPase in the cytotoxicity of hexachlorocyclohexane (HCH) on Ehrlich Ascites tumor (EAT) cells has been studied. HCH caused dose dependent cell death as measured by trypan blue exclusion and lactate dehydrogenase (LDH) leakage from the cells. HCH induced oxidative stress in EAT cells which was characterized by glutathione depletion, lipid peroxidation (LPO), reactive oxygen species (ROS) production and inhibition of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT). Protective effect of antioxidants on HCH induced oxidative stress was assessed, among the antioxidants used only quercetin inhibited HCH-induced LPO and ROS production as well as cell death whereas alpha -tocopherol, ascorbic acid and BHA inhibited LPO but not cell death. Inhibition of membrane bound Na+,K+-ATPase was a characteristic feature of HCH cytotoxicity in EAT cells. Experimental evidence indicates that HCH-induced cell death involves oxidative stress due to ROS production and membrane perturbation in EAT cells.
Srivastava
Anup
A
Department of Food Protectants and Infestation Control, Central Food Technological Research Institute, Mysore 570020, India. anup_s100@yahoo.com
Shivanandappa
T
T
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism / Q000473:pathology; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007306:Insecticides; D017382:Reactive Oxygen Species; D001556:Hexachlorocyclohexane; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione