• cyanide;
  • cytochrome oxidase;
  • mitochondrial respiration;
  • brain mitochondria;
  • mouse


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.