Comparison of brain mitochondrial cytochrome c oxidase activity with cyanide LD50 yields insight into the efficacy of prophylactics
Article first published online: 13 JUL 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 33, Issue 1, pages 50–55, January 2013
How to Cite
Marziaz, M. L., Frazier, K., Guidry, P. B., Ruiz, R. A., Petrikovics, I. and Haines, D. C. (2013), Comparison of brain mitochondrial cytochrome c oxidase activity with cyanide LD50 yields insight into the efficacy of prophylactics. J. Appl. Toxicol., 33: 50–55. doi: 10.1002/jat.1709
- Issue published online: 29 NOV 2012
- Article first published online: 13 JUL 2011
- Manuscript Accepted: 17 MAY 2011
- Manuscript Revised: 16 MAY 2011
- Manuscript Received: 25 FEB 2011
- cytochrome c oxidase;
- mouse studies
Cyanide inhibits cytochrome c oxidase, the terminal oxidase of the mitochondrial respiratory pathway, therefore inhibiting the cell oxygen utilization and resulting in the condition of histotoxic anoxia. The enzyme rhodanese detoxifies cyanide by utilizing sulfur donors to convert cyanide to thiocyanate, and new and improved sulfur donors are actively sought as researchers seek to improve cyanide prophylactics. We have determined brain cytochrome c oxidase activity as a marker for cyanide exposure for mice pre-treated with various cyanide poisoning prophylactics, including sulfur donors thiosulfate (TS) and thiotaurine (TT3). Brain mitochondria were isolated by differential centrifugation, the outer mitochondrial membrane was disrupted by a maltoside detergent, and the decrease in absorbance at 550 nm as horse heart ferrocytochrome c (generated by the dithiothreitol reduction of ferricytochrome c) was oxidized was monitored. Overall, the TS control prophylactic treatment provided significant protection of the cytochrome c oxidase activity. The TT3-treated mice showed reduced cytochrome c oxidase activity even in the absence of cyanide. In both treatment series, addition of exogenous Rh did not significantly enhance the prevention of cytochrome c oxidase inhibition, but the addition of sodium nitrite did. These findings can lead to a better understanding of the protection mechanism by various cyanide antidotal systems. Copyright © 2011 John Wiley & Sons, Ltd.