Inhibition of cadmium-induced oxidative injury in rat primary astrocytes by the addition of antioxidants and the reduction of intracellular calcium

Chung Shi Yang, Bo Cheng Tzou, Yu Peng Liu, May Jywan Tsai, Song Kun Shyue, Shun Fen Tzeng

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57 Citations (Scopus)

Abstract

Exposure of the brain to cadmium ions (Cd2+) is believed to lead to neurological disorders of the central nervous system (CNS). In this study, we tested the hypothesis that astrocytes, the major CNS-supporting cells, are resistant to Cd2+-induced injury compared with cortical neurons and microglia (CNS macrophages). However, treatment with CdCl2 for 24 h at concentrations higher than 20 μM substantially induced astrocytic cytotoxicity, which also resulted from long-term exposure to 5 μM of CdCl2. Intracellular calcium levels were found to rapidly increase after the addition of CdCl2 into astrocytes, which led to a rise in reactive oxygen species (ROS) and to mitochondrial impairment. In accordance, preexposure to the extracellular calcium chelator EGTA effectively reduced ROS production and increased survival of Cd2+-treated astrocytes. Adenovirus-mediated transfer of superoxide dismutase (SOD) or glutathione peroxidase (GPx) genes increased survival of Cd2+-exposed astrocytes. In addition, increased ROS generation and astrocytic cell death due to Cd 2+ exposure was inhibited when astrocytes were treated with the polyphenols compound ellagic acid (EA). Taken together, Cd2+-induced astrocytic cell death resulted from disrupted calcium homeostasis and an increase in ROS. Moreover, our findings demonstrate that enhancement of the activity of intracellular antioxidant enzymes and supplementation with a phenolic compound, a natural antioxidant, improves survival of Cd 2+-primed astrocytes. This information provides a useful approach for treating Cd2+-induced CNS neurological disorders.

Original languageEnglish
Pages (from-to)825-834
Number of pages10
JournalJournal of Cellular Biochemistry
Volume103
Issue number3
DOIs
Publication statusPublished - 2008 Feb 15

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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