Intramuscular administration of glyoxylate rescues swine from lethal cyanide poisoning and ameliorates the biochemical sequalae of cyanide intoxication.

This article focuses on evaluating glyoxylate, an endogenous metabolite, as a novel intramuscular antidote for cyanide poisoning using a swine model that approximates human physiology. Glyoxylate administration significantly improved survival (83% vs. 12% in controls), restored clinical parameters such as respiration and oxygenation, and normalized citric acid cycle metabolites disrupted by cyanide toxicity. Unlike existing FDA-approved cyanide antidotes that rely on intravenous chelation, glyoxylate acts through both cyanide binding and modulation of intracellular and extracellular redox balances, as evidenced by changes in lactate:pyruvate and cysteine:cystine ratios. Pharmacokinetic studies showed rapid absorption and metabolism of glyoxylate without acute toxicity in rats, supporting its potential for rapid intramuscular delivery in mass casualty scenarios. These findings suggest glyoxylate may expand current cyanide countermeasures by addressing metabolic and redox disturbances beyond cyanide chelation.