Cyanide Beyond Toxicity: A Systematic Review of Its Effects on Vascular Function

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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.

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