The effects of cyanide on brain mitochondrial cytochrome oxidase and respiratory activities

✍ Scribed by John C. Pettersen; Steven D. Cohen

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 714 KB
• Volume: 13
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.2550130104

✦ Synopsis

Abstract

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.