is vitamin C a antidote for cyanide poisoining?

is methylene blue a antidote?











ArticlePDF Available
Reversal of cyanide inhibition of cytochrome C oxidase by the auxiliary substrate nitric oxide: An endogenous antidote to cyanide poisoning?
January 2004Journal of Biological Chemistry 278(52):52139-45

Nitric oxide (NO) is shown to overcome the cyanide inhibition of cytochrome c oxidase in the presence of excess ferrocytochrome c and oxygen. Addition of NO to the partially reduced cyanide-inhibited form of the bovine enzyme is shown by electron paramagnetic resonance spectroscopy to result in substitution of cyanide at ferriheme a3 by NO with reduction of the heme. The resulting nitrosylferroheme a3 is a 5-coordinate structure, the proximal bond to histidine having been broken. NO does not simply act as a reversibly bound competitive inhibitor but is an auxiliary substrate consumed in a catalytic cycle along with ferrocytochrome c and oxygen. The implications of this observation with regard to estimates of steady-state NO levels in vivo is discussed. Given the multiple sources of NO available to mitochondria, the present results appear to explain in part some of the curious biomedical observations reported by other laboratories; for example, the kidneys of cyanide poisoning victims surprisingly exhibit no significant irreversible damage, and lethal doses of potassium cyanide are able to inhibit cytochrome c oxidase activity by only approximately 50% in brain mitochondria.












现在是定义“氰化物”的好时机。氰化物是带负电荷的离子,CN,但在生理pH 7.4时,它以氰化氢的形式存在,HCN。氰化物一旦进入血液,大多数(92-99%)会与红细胞中的血红蛋白结合。从那里它被带到身体的组织,在那里它与一种叫做细胞色素氧化酶的酶结合,阻止细胞使用氧气。氰化物中毒的症状和体征包括头痛、呼吸困难和呕吐、昏迷和死亡。氰化物中毒后康复的人通常不会受到任何长期影响。











Cyanide Poisoning
Scheele was the first to isolate Hydrogen cyanide in 1782 then went on to show its toxic effects by accidentally becoming its victim. Alexandra looks...
19 April 2006

Murder, terrorism and suicide...These are the scenarios generally associated with cyanide poisoning. One would hope these are rare occurrences but incidences of cyanide poisoning are all too common and increasing.Toxic_icon The reason for this is that when man-made polymers such as polyacrylonitrile, nylon and melamine are burned they produce hydrogen cyanide (HCN) gas.

These substances are used in clothes and furnishings and so HCN gas can be produced during a fire and anyone near the fire can is exposed to it. Hydrogen cyanide was first isolated in 1782 by Scheele. He later went on to provide a practical demonstration of its toxic effects by accidentally becoming its victim. It is often associated with the smell of bitter almonds but in fact only about 40% of people can smell it.

Cyanide is naturally present in everyone's blood in very small amounts, and people who smoke tend to have more in their blood than people who don't.

This would be a good moment to define 'cyanide'. Cyanide is the negatively charged ion, CN- but at physiological pH 7.4, when unbound, this is in the form of hydrogen cyanide, HCN. Once cyanide is taken into the blood stream the majority (92-99%) is found bound to hemoglobin (Hb) in red blood cells. From there it is taken to the body's tissues where it binds to an enzyme called cytochrome oxidase and stops cells from being able to use oxygen. The signs and symptoms of cyanide poisoning range from headache, difficulty in breathing and vomiting to unconsciousness and death. People who have recovered from cyanide poisoning do not usually suffer any long-term effects.

Cyanide can be metabolized rapidly and is generally converted to thiocyanate by an enzyme called rhodanese. Thiocyanate is much less toxic than cyanide and the body can then get rid of this. But (there had to be a but!) the enzyme needs another chemical, thiosulfate, to be able to do this and this can be used up quite quickly.

Cyanide and cyanide containing compounds are used in lots of industrial processes such as electroplating, chemical synthesis and fumigation. Some food types contain compounds called cyanogenic glycosides which can be converted to cyanide in the body; these include cassava roots, lima beans and bamboo shoots. In addition drugs such as sodium nitroprusside, sometimes used for the treatment of hypertension and Laetrile, an anti-cancer agent, also release cyanide into the circulation.

Cyanide salts are the forms which historically have been used for suicide and murder. They can't be bought as easily now by the public and so they aren't used much for this now. Nevertheless there are recent cases, for example in 1982 seven people in Chicago were killed by Tylenol tablets (painkillers) which were spiked with cyanide salts.

Figure 1: The effects of cyanide within the body. Hydrogen cyanide gas (HCN) is inhaled and locks onto haemoglobin, the oxygen-carrying molecule in red blood cells (bottom right). It is then distributed via the bloodstream to cells throughout the body where it binds to an important metabolic enzyme called cytochrome oxidase (bottom left), preventing cells from using oxygen to produce energy. In this way cyanide effectively chemically asphyxiates the body.
Figure 1: The effects of cyanide within the body. Hydrogen cyanide gas (HCN) is inhaled and locks onto haemoglobin, the oxygen-carrying molecule in red blood cells (bottom right). It is then distributed via the bloodstream to cells throughout the body where it binds to an important metabolic enzyme called cytochrome oxidase (bottom left), preventing cells from using oxygen to produce energy. In this way cyanide effectively chemically asphyxiates the body.
There are antidotes available for cyanide poisoning but they can have bad side effects or be toxic themselves. For example some drugs act to change normal hemoglobin to another form called methemoglobin, as cyanide has a high affinity for this type of hemoglobin, which binds the cyanide and stops it from reaching the tissues.

Unfortunately oxidized hemoglobin does not bind oxygen and so obviously it is not desirable to have too much of this form present. Extra thiosulfate can also be given so that more cyanide can be metabolized, this is often used with methemoglobin formers. Cobalt (II) compounds form cyanide complexes and these are used but they are highly toxic. Hydroxycobalamin (Vitamin B12a) which forms cyanocobalamin (Vitamin B12) has lower toxicity but it is not widely available. Due to the toxicity of these drugs it is important they are given in doses related to the amount of cyanide in the body.

So, yet another reason to make sure you've checked the batteries work in your smoke alarm!

Cyanide Poisoning | Science Features | Naked Scientists




。2018年5月1日,124(5):1164 - 1176。doi: 10.1152 / japplphysiol.00967.2017。Epub 2018年2月8日



在成年左心室小鼠心肌细胞中,暴露于葡萄糖剂量依赖性的氰化钠(NaCN)可降低收缩幅度,在100时达到约80%的最大抑制作用。NaCN暴露10min显著降低收缩和细胞内Ca2+浓度([Ca2+]i)的瞬时振幅,收缩期而非舒张期[Ca2+]i,以及最大l型Ca2+电流(ICa)振幅,提示急性改变[Ca2+]i稳态主要是观察到的兴奋-收缩异常的原因。此外,NaCN去极化静息膜电位(Em)、降低动作电位(AP)振幅、AP持续时间在50% (APD50)和90%复极化(APD90)延长,去极化激活的K+电流被抑制,但对Na+-Ca2+交换电流(INaCa)无影响。NaCN并不影响细胞三磷酸腺苷水平但线粒体膜电位去极化的(ΔΨm)和增加超氧化物(O2·)的水平。

亚甲蓝(MB;20µg / ml)添加3分钟后NaCN恢复收缩和[Ca2 +]我瞬时振幅,收缩期[Ca2 +]i,AP振幅,APD50, APD90, ICa, depolarization-activated K +电流,ΔΨm和O2·——对正常水平。




J Appl Physiol (1985)
. 2018 May 1;124(5):1164-1176. doi: 10.1152/japplphysiol.00967.2017. Epub 2018 Feb 8.
Methylene blue counteracts cyanide cardiotoxicity: cellular mechanisms

In adult left ventricular mouse myocytes, exposure to sodium cyanide (NaCN) in the presence of glucose dose-dependently reduced contraction amplitude, with ~80% of maximal inhibitory effect attained at 100 µM. NaCN (100 µM) exposure for 10 min significantly decreased contraction and intracellular Ca2+ concentration ([Ca2+]i) transient amplitudes, systolic but not diastolic [Ca2+]i, and maximal L-type Ca2+ current ( ICa) amplitude, indicating acute alteration of [Ca2+]i homeostasis largely accounted for the observed excitation-contraction abnormalities. In addition, NaCN depolarized resting membrane potential ( Em), reduced action potential (AP) amplitude, prolonged AP duration at 50% (APD50) and 90% repolarization (APD90), and suppressed depolarization-activated K+ currents but had no effect on Na+-Ca2+ exchange current ( INaCa). NaCN did not affect cellular adenosine triphosphate levels but depolarized mitochondrial membrane potential (ΔΨm) and increased superoxide (O2·-) levels.

Methylene blue (MB; 20 µg/ml) added 3 min after NaCN restored contraction and [Ca2+]i transient amplitudes, systolic [Ca2+]i, Em, AP amplitude, APD50, APD90, ICa, depolarization-activated K+ currents, ΔΨm, and O2·- levels toward normal.

We conclude that MB reversed NaCN-induced cardiotoxicity by preserving intracellular Ca2+ homeostasis and excitation-contraction coupling ( ICa), minimizing risks of arrhythmias ( Em, AP configuration, and depolarization-activated K+ currents), and reducing O2·- levels. NEW & NOTEWORTHY Cyanide poisoning due to industrial exposure, smoke inhalation, and bioterrorism manifests as cardiogenic shock and requires rapidly effective antidote.

In the early stage of cyanide exposure, adenosine triphosphate levels are normal but myocyte contractility is reduced, largely due to alterations in Ca2+ homeostasis because of changes in oxidation-reduction environment of ion channels. Methylene blue, a drug approved by the U.S. Food and Drug Administration, ameliorates cyanide toxicity by normalizing oxidation-reduction state and Ca2+ channel function.

Keywords: calcium; cyanide cardiotoxicity; ion channels; mitochondria; reactive oxygen species.

Methylene blue counteracts cyanide cardiotoxicity: cellular mechanisms - PubMed