Smoke inhalation is a common cause of cyanide poisoning during fires, resulting in injury and even death. In many cases of smoke inhalation, cyanide has increasingly been recognized as a significant toxicant. The diagnosis of cyanide poisoning remains very difficult, and failure to recognize it may result in inadequate or inappropriate treatment. Findings suggesting cyanide toxicity include the following: (a) a history of enclosed-space fire; (b) any alteration in the level of consciousness; (c) any cardiovascular changes (particularly inexplicable hypotension); and (d) elevated plasma lactate. The feasibility and safety of empiric treatment with hydroxocobalamin for fire smoke victims have been reported in the literature. On the basis of a literature review and a panel discussion, a group of European experts has proposed emergency management protocols for cyanide toxicity in fire smoke victims.

SummaryThe effect of cyanide on the respiration of living cells makes possible the differentiation between and the description of two types of respiratory systems.(1) The cyanide‐sensitive respiration may be identified with the Warburg‐Keilin respiratory system. The normal variation in Qo1 between different organs, organisms, developmental stages (in certain enumerated cases) and random variations among samples of the same tissue, seem largely to be accountable by differences in the activity of this system. The rate of oxygen consumption by this system varies over a wide range of values, and accounts for about 90% of the maximum possible respiratory rate of most actively aerobic tissues and organisms. It seems likely (on the basis of the available data) that the cyanide‐sensitive system tends most actively to oxidize carbohydrates and other metabolites that have a similarly high water‐solubility and O/C ratio. Thus, cyanide‐sensitive respiration is characterized by a respiratory quotient of about 1.0. The Warburg‐Keilin system also appears to be the more sensitive (of the two) to variations in temperature and po2.(2) The cyanide‐stable respiration may be identified with the yellow enzyme or flavoprotein. Its activity is relatively small and constant from organ to organ and from organism to organism (within certain groups), as compared with the activity of the cyanide‐sensitive system. It seems likely that the metabolic substrates of this respiratory system (in vivo) are restricted, in the main, to fatty compounds and other substances that have a similarly low O/C ratio. Thus, the cyanide‐stable respiration is characterized by a respiratory quotient of 0.8 or less.Hence, since most variations in the total rate of respiration are mainly due to variations in the activity of the cyanide‐sensitive system alone, percentage inhibition by cyanide (i.e. “cyanide‐sensitivity”) increases with the normal rate of respiration. Therefore, this value is no index of the relative activity of the two systems unless the substrate environment and other influential conditions are specified.Certain intrinsic properties of the Warburg‐Keilin system are elucidated by partial inhibition of this system. It is shown thereby that the inhibitory effect of cyanide is related to the extent of saturation of the dehydrogenase with its substrate. When the dehydrogenase is only partially saturated or “covered”, the respiratory rate is reduced only by high cyanide concentrations. Thus, under such circumstances, part of the oxidase may be inactivated by a low concentration of cyanide without affecting the rate of respiration. However, such a cyanide concentration prevents the rise in respiratory rate that normally follows the restoration of the dehydrogenase to complete saturation by the addition of substrate to the medium. Thus, in this case we again note that the percentage inhibition by cyanide increases with the original (i.e. cyanide‐free) rate of respiration.It appears therefore that the respiratory systems that can be distinguished by means of cyanide‐sensitivity are to a large degree independent of each other. It has frequently been suggested that the two systems present alternative paths for the oxidation of any given metabolite. The amount of oxidative activity of each system would then depend on their relative concentrations in the cell and on their relative oxidative tendencies, i.e. redox potentials. If this were so, we would expect that the ratio of their activities would be constant regardless of the nature or concentration of the metabolite present in the medium. Furthermore, if the activity of one of these systems be curtailed (e.g. by cyanide), it follows that the insensitive system would become more active since it would then be exposed to a greater portion of the “reduction potential”) which is produced by the metabolite and its dehydrogenase.It does not seem likely, ‐therefore, that this is a valid interpretation of the interrelationships of t

Although exposure to cyanogenic plants or cyanide during pregnancy has adverse effects, no teratological study with cyanide has been conducted in goats or any other ruminant. The objective of the present study was to evaluate the effects of the maternal exposure to potassium cyanide (KCN) during pregnancy on both dams and offspring and furthermore, to develop a model for prenatal toxicological studies in ruminants. Twenty-six pregnant goats were allocated into four groups and given 0, 1.0, 2.0, or 3.0mg KCN/kg body weight per day orally (administered via twice-daily gavage) from Day 24 of pregnancy to term. However, one control dam and another from the 3.0mg KCN/kg per day group were sacrificed on Day 120. At birth, the kids were examined carefully for gross abnormalities. Three months after birth, the male kids and one dam from each group were sacrificed for histopathological study. Although clinical signs of poisoning were observed in dams, cyanide treatment did not alter the length of gestation or the number of live kids. Two prognata kids were born in the 3.0mg KCN/kg group, and one dam from the same group aborted two fetuses. There were histological lesions only in the KCN-treated dam (and its fetuses) sacrificed on Day 120; these consisted of an increased number of resorption vacuoles of thyroid follicular colloid, and status spongiosis of nervous white matter. This study proposes a new animal model for teratogenic trials that could be important to evaluate the effects of chemicals throughout pregnancy in goats and potentially other ruminants.

ABSTRACT Cyanide is widely recognized for its potent toxicity, yet evidence shows that concentrations below 1 μM may enhance cytochrome c oxidase activity and have a regulatory function. Recent findings also demonstrate that mammalian cells, including endothelial cells, produce cyanide endogenously, where it can modulate mitochondrial bioenergetics. However, the vascular implications of this endogenous production remain unexplored. The review addresses this gap and evaluates the vascular effects of glycine, a proposed substrate for endogenous cyanide synthesis. This systematic review was conducted in accordance with PRISMA 2020 guidelines. Seventy‐eight studies were included. Eligible studies with quantifiable vascular outcomes were screened and synthesized. Exogenous cyanide elicited vascular responses through mitochondrial inhibition, modulation of calcium signalling and interference with the soluble guanylyl cyclase/cyclic guanosine monophosphate pathway. Subchronic low‐dose in vivo cyanide exposure reduced contractions and enhanced relaxation in endothelium‐denuded aortic rings. Collectively, evidence indicates a biphasic pattern: high concentrations are cytotoxic, whereas low concentrations may exert protective/regulatory effects. Low‐dose cyanide may have therapeutic potential in managing vascular disorders associated with endothelial dysfunction. Determining an effective and safe dosage range is crucial, and further studies are needed to clarify the role of endogenous cyanide in regulating vascular function.

Cyanide is one of the oldest known poisons in human history. In the 1980s, seminal work began to elucidate the broad cellular mechanisms of cyanide toxicity beyond its canonical inhibition of cytochrome c oxidase. In the 1990s, endogenous metabolites were shown to sequester cyanide, and these became promising avenues for the development of a cyanide antidote. However, an FDA-approved metabolite-based cyanide antidote did not come to fruition. More recently, in the past 10 years, advances in mass spectrometry-based metabolomics profiling, subcellular drug targeting, and genome editing have brought fresh perspectives to the concept of a metabolism-based cyanide antidote. Here, we review the mechanisms of cyanide toxicity with a focus on intermediary metabolism. We discuss the current state of our knowledge and gaps in our understanding of the metabolic mechanisms that contribute to cyanide poisoning, in addition to highlighting recent findings that break new ground in the field. We present the theory of redirecting intermediary metabolism to counteract cyanide poisoning: while cyanide shifts metabolism from oxidative phosphorylation to glycolysis, the metabolome encompasses hundreds of pathways; thus, potential therapeutic opportunities may reside in activating metabolism into other pathways. Potential approaches to targeting metabolism as a therapeutic intervention for cyanide poisoning will also be discussed. These targets represent an opportunity for a significant paradigm shift from current FDA-approved treatments, which chelate the chemical toxicant but do not reverse the broad spectrum of cellular and metabolic damage caused by cyanide, to a treatment that may improve the long-term effects of cyanide poisoning.

Respiration in blue-green algae. The low rate of endogenous respiration exhibited by the blue-green algae Anacystis nidulans and Phormidium luridum was not increased by the addition of respiratory substrates. However, endogenous respiration was inhibited by low concentrations of cyanide and by high carbon monoxide tensions. In addition, the uncouplers dinitrophenol and carbonyl cyanide p-trifluoromethoxyphenylhydrazone both stimulated the respiratory rate. The transition of cells from the aerobic steady state to anaerobiosis was accompanied by a decrease in the concentration of cellular nicotinamide adenine dinucleotide phosphate (NADP(+)) and adenosine triphosphate (ATP), whereas the concentration of nicotinamide adenine dinucleotide (NAD(+)) was unchanged. Concomitant with the metabolite decreases were stoichiometric increases io reduced NADP(+) (NADPH), adenosine diphosphate, and adenosine monophosphate. A decrease in ATP was also observed after the addition of uncouplers. These data are interpreted as evidence for the association of oxidative phosphorylation with the oxidation of NADP(+)-linked substrates in these algae.

Properties of mitochondria isolated from cyanide-sensitive and cyanide-stimulated cultures of Acanthamoeba castellanii. 1. Mitochondria isolated from cultures of Acanthamoeba castellanii exhibit respiratory control and oxidize alpha-oxoglutarate, succinate and NADH with ADP:O ratios of about 2.4, 1.4 and 1.25 respectively. 2. Mitochondria from cultures of which the respiration was stimulated up to 50% by 1mm-cyanide (type-A mitochondria) and from cyanide-sensitive cultures (type-B mitochondria) had similar respiratory-control ratios and ADP:O ratios. 3. State-3 rates of respiration were generally more cyanide-sensitive than State-4 rates, and the respiration of type-A mitochondria was more cyanide-resistant than that of type-B mitochondria. 4. Salicylhydroxamic acid alone had little effect on respiratory activities of either type of mitochondria, but when added together with cyanide, irrespective of the order of addition, inhibition was almost complete. 5.