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Role of Oxidative Stress, Apoptosis, and Intracellular Homeostasis in Primary Cultures of Rat Proximal Tubular Cells Exposed to Cadmium

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Abstract

Cadmium (Cd) is a known nephrotoxic element. In this study, the primary cultures of rat proximal tubular (rPT) cells were treated with low doses of cadmium acetate (2.5 and 5 µM) to investigate its cytotoxic mechanism. A progressive loss in cell viability, together with a significant increase in the number of apoptotic and necrotic cells, were seen in the experiment. Simultaneously, elevation of intracellular [Ca2+]i and reactive oxygen species (ROS) levels, significant depletion of mitochondrial membrane potential(Δ Ψ) and cellular glutathione (GSH), intracellular acidification, and inhibition of Na+, K+-ATPase and Ca2+-ATPase activities were revealed in a dose-dependent manner during the exposure, while the cellular death and the apoptosis could be markedly reversed by N-acetyl-l-cysteine (NAC). Also, the calcium overload and GSH depletion were significantly affected by NAC. In conclusion, exposure of rPT cells to low-dose cadmium led to cellular death, mediated by an apoptotic and a necrotic mechanism. The apoptotic death might be the chief mechanism, which may be mediated by oxidative stress. Also, a disorder of intracellular homeostasis induced by oxidative stress and mitochondrial dysfunction is a trigger of apoptosis in rPT cells.

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Acknowledgements

This work was supported by the National Nature Science Foundation of China (no. 30440050 and 30571364).

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Authors and Affiliations

  1. College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou, 225009, People’s Republic of China

    Lin Wang, Jin Cao, Dawei Chen, Xuezhong Liu, Hao Lu & Zongping Liu

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  1. Lin Wang
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  2. Jin Cao
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  3. Dawei Chen
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  4. Xuezhong Liu
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  6. Zongping Liu
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Correspondence to Zongping Liu.

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Wang, L., Cao, J., Chen, D. et al. Role of Oxidative Stress, Apoptosis, and Intracellular Homeostasis in Primary Cultures of Rat Proximal Tubular Cells Exposed to Cadmium. Biol Trace Elem Res 127, 53–68 (2009). https://doi.org/10.1007/s12011-008-8223-7

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  • DOI: https://doi.org/10.1007/s12011-008-8223-7

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