In vitro protection by pyruvate against cadmium-induced cytotoxicity in hippocampal HT-22 cells
Article first published online: 30 AUG 2013
Copyright © 2013 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
How to Cite
Poteet, E., Winters, A., Xie, L., Ryou, M.-G., Liu, R. and Yang, S.-H. (2013), In vitro protection by pyruvate against cadmium-induced cytotoxicity in hippocampal HT-22 cells. J. Appl. Toxicol.. doi: 10.1002/jat.2913
- Article first published online: 30 AUG 2013
- Manuscript Accepted: 2 JUL 2013
- Manuscript Revised: 1 JUL 2013
- Manuscript Received: 27 FEB 2013
- National Institutes of Health. Grant Numbers: R01NS054687 (SY), R01NS054651 (SY)
Cadmium is a toxic metal with no biological function in higher-order mammals. Humans are exposed to cadmium environmental contamination and the mechanism underlying the cadmium's cytotoxicity is unclear. To better understand this mechanism, we employed murine hippocampal HT-22 cells to test the in vitro effects of cadmium toxicity. Our study indicated that cadmium inhibits both mitochondria oxidative phosphorylation and glycolysis. In turn, this causes depolarization of mitochondrial membrane potential, increase of superoxide production and decrease of ATP generation. Furthermore, we demonstrated that the detrimental action of cadmium in bioenergetics could be mitigated by pyruvate, an intermediate metabolic product. Pyruvate decreased superoxide production, maintained mitochondrial membrane potential, restored glycolysis, mitigated the decrease in cellular ATP and attenuated cadmium cytotoxicity. Our study provides the first evidence that pyruvate might offer promising therapy for cadmium poisoning. Copyright © 2013 John Wiley & Sons, Ltd.