Antioxidant effect of zinc and zinc-metallothionein in the acute cytotoxicity of hydrogen peroxide in Ehrlich ascites tumour cells.
This study was concerned with the role of zinc (Zn) and zinc-metallothionein (Zn-MT) in oxidative stress. Hydrogen peroxide-induced oxidative injury was examined in Ehrlich ascites tumour cells isolated from control host mice, mice pretreated with 10 mg/kg ZnSO4 (i.p.) to increase cellular Zn/Zn-MT levels, and mice exposed to Zn-deficient diet to reduce the cellular Zn/Zn-MT levels. The results of the present study showed that Ehrlich cells with seven-fold differences in Zn-MT concentrations could be obtained by manipulating the Zn status of host mice and that high Zn and Zn-MT levels can make Ehrlich cells more resistant to H2O2-induced oxidative injury (cell viability, lipid peroxidation, [Ca2+]i) while cells with reduced Zn/Zn-MT levels were more susceptible to this treatment. H2O2 treatment resulted in oxidation of MT thiolate groups and loss of its metal binding capacity with translocation of Zn released from oxidized MT to other cellular sites. Preincubation of Ehrlich cells with ZnSO4 in vitro also conferred some degree of resistance to H2O2 toxicity, suggesting the inherent antioxidative property of Zn ions. These data suggested that Zn-MT can be considered as an antioxidant by virtue of its thiolate groups and its Zn ions that are released in the presence of oxidative stress.
Suntres
Zacharias E
ZE
Medical Sciences Division, Northern Ontario School of Medicine, Lakehead University, 955 Oliver Road, Thunder Bay, Ont., Canada P7B 5E1. Electronic address: Zacharias.Suntres@NorMed.ca.
Lui
Edmund M K
EMK
Department of Physiology and Pharmacology, University of Western Ontario, London, Ont., Canada N6A-5C1.
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008668:Metallothionein / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009368:Neoplasm Transplantation; D011485:Protein Binding; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*
D000975:Antioxidants; C021267:zinc thionein; D003300:Copper; D008668:Metallothionein; D006861:Hydrogen Peroxide; D005978:Glutathione; D015032:Zinc; D002118:Calcium