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Zinc pretreatment prevents hepatic stellate cells from cadmium-produced oxidative damage

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Abstract

Pretreatment with zinc produces tolerance to several cadmium toxic effects. This study was performed to further elucidate the mechanism of zinc-induced tolerance to cadmium cytotoxicity in a rat hepatic stellate cell line (CFSC-2G). Twenty four hours after seeding, cells were treated with 60 μmol/L ZnCl2 for 24 h. Following zinc pretreatment, cells were exposed to 3 μmol/L and 5 μmol/L CdCl2 for an additional 24 h. The toxicity of cadmium was significantly reduced in the zinc-pretreated cells. Zinc pretreatment produced a decrease in lipid peroxidation damage of cadmiumtreated cells. Glutathione cell content diminished 33% and 43% as a result of 3 μmol/L and 5 μmol/L CdCl2 treatment, respectively. Cell pretreatment with zinc recovered glutathione content at control cells level. Catalase and glutathione peroxidase activities were also recovered to control values with zinc pretreatment. Cadmium (5 μmol/L) was able to induce 39% the expression of α1 collagen (I) gene after 1 h treatment, while zinc pretreatment prevented this cadmium profibrogenic effect. We also examined the production of heat shock protein 70 (Hsp70) as a cellular response to oxidative stress produced by cadmium. By Western blot analysis, a 1.3 and 3 times increment in Hsp70, with 3 μmol/L and 5 μmol/L CdCl2 treatment, respectively, was observed. Zinc pretreatment prevented the production of Hsp70. Metallothionein-II (MT-II) gene expression was induced by cadmium, but the induction was unaffected with zinc pretreatment. These data suggest that zinc-induced protection against the cytotoxicity of cadmium in stellate cells may be related to the maintenance of normal redox balance inside the cell.

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Abbreviations

Cd:

cadmium

CFSC-2G:

hepatic stellate cell-line

GSH:

glutathione

Hsp:

heat shock protein

MT-II:

metallothionein-II

SOD:

superoxide dismutase

SDS-PAGE:

sodium dodecyl sulfate-polyacrylamide gel electrophoresis

Zn:

zinc

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Authors and Affiliations

  1. Laboratorio de Fisiología Celular, Departamento de Ciencias de la Salud, DCBS, Universidad Autónoma Metropolitana-Iztapalapa, Apdo. Postal 55-535, 09340, México, D.F., México

    V. Souza, M. del C. Escobar, L. Bucio, E. Hernández & M. C. Gutiérrez-Ruiz

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  1. V. Souza
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  2. M. del C. Escobar
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  3. L. Bucio
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  4. E. Hernández
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  5. M. C. Gutiérrez-Ruiz
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Correspondence to M. C. Gutiérrez-Ruiz.

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Souza, V., Escobar, M.d.C., Bucio, L. et al. Zinc pretreatment prevents hepatic stellate cells from cadmium-produced oxidative damage. Cell Biol Toxicol 20, 241–251 (2004). https://doi.org/10.1023/B:CBTO.0000038462.39859.2f

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  • DOI: https://doi.org/10.1023/B:CBTO.0000038462.39859.2f

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