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In vitro protection by pyruvate against cadmium‐induced cytotoxicity in hippocampal HT‐22 cells
Author(s) -
Poteet Ethan,
Winters Ali,
Xie Luokun,
Ryou MyoungGwi,
Liu Ran,
Yang ShaoHua
Publication year - 2014
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2913
Subject(s) - cadmium , cytotoxicity , glycolysis , mitochondrion , cadmium poisoning , reactive oxygen species , chemistry , bioenergetics , biochemistry , superoxide , adenosine triphosphate , oxidative phosphorylation , microbiology and biotechnology , biology , in vitro , metabolism , enzyme , organic chemistry
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.