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The effects of cyanide on brain mitochondrial cytochrome oxidase and respiratory activities
Author(s) -
Pettersen John C.,
Cohen Steven D.
Publication year - 1993
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.2550130104
Subject(s) - cytochrome c oxidase , cyanide , mitochondrion , respiration , oxidase test , cytochrome c , cytochrome , biochemistry , chemistry , in vivo , respiratory chain , pharmacology , enzyme , biology , anatomy , inorganic chemistry , microbiology and biotechnology
Brain mitochondrial cytochrome oxidase and respiratory activities were compared after in vivo and in vitro exposure to cyanide. For the in vivo studies, mice were exposed to a non‐lethal (4 mg kg −1 ) or lethal (20 mg kg −1 ) dose of KCN. From these mice, purified brain mitochondria were prepared and cytochrome oxidase and respiratory activities measured. Results of these experiments revealed greater inhibition of cytochrome oxidase activity following a lethal (20 mg kg −1 ) than a non‐lethal (4 mg kg −1 ) KCN dose (57 and 45% inhibition, respectively). Respiration states 3 and 4 of brain mitochondria prepared from mice that received 4 mg kg −1 KCN were inhibted by 15 and 20%, respectively. In mice that received a lethal 20 mg kg −1 KCN dose, respiration states 3 and 4 were each inhibited by ca. 30% ( P <0.05). In vitro , mitochondrial cytochrome oxidase activity was inhibited in a concentration‐dependent fashion at cyanide concentrations of 10 −6 –10 −2 M. A biphasic inhibition of ADP‐stimulated (state 3) respiration was observed. Cyanide concentrations of 10 −6 –10 −4 M produced only a 25% inhibition of respiration state 3, whereas 10 −3 M produced 80% inhibition. Because this dramatic inhibition only occurred at cyanide concentrations that caused >50% inhibition of mitochondrial cytochrome oxidase activity, these findings suggest that a large proportion of cytochrome oxidase activity may be functional reserve and that cyanide poisoning likely involves other mechanisms in addition to inhibition of cytochrome oxidase.