title: Toxicokinetic profiles of α-ketoglutarate cyanohydrin, a cyanide detoxification product, following exposure to potassium cyanide.
abstract: Poisoning by cyanide can be verified by analysis of the cyanide detoxification product, α-ketoglutarate cyanohydrin (α-KgCN), which is produced from the reaction of cyanide and endogenous α-ketoglutarate. Although α-KgCN can potentially be used to verify cyanide exposure, limited toxicokinetic data in cyanide-poisoned animals are available. We, therefore, studied the toxicokinetics of α-KgCN and compared its behavior to other cyanide metabolites, thiocyanate and 2-amino-2-thiazoline-4-carboxylic acid (ATCA), in the plasma of 31 Yorkshire pigs that received KCN (4mg/mL) intravenously (IV) (0.17 mg/kg/min). α-KgCN concentrations rose rapidly during KCN administration until the onset of apnea, and then decreased over time in all groups with a half-life of 15 min. The maximum concentrations of α-KgCN and cyanide were 2.35 and 30.18 μM, respectively, suggesting that only a small fraction of the administered cyanide is converted to α-KgCN. Although this is the case, the α-KgCN concentration increased >100-fold over endogenous concentrations compared to only a three-fold increase for cyanide and ATCA. The plasma profile of α-KgCN was similar to that of cyanide, ATCA, and thiocyanate. The results of this study suggest that the use of α-KgCN as a biomarker for cyanide exposure is best suited immediately following exposure for instances of acute, high-dose cyanide poisoning.
authors.affiliation: Department of Chemistry and Biochemistry, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Brendan L
authors.initials: BL
authors.lastname: Mitchell
authors.forename: Raj K
authors.initials: RK
authors.lastname: Bhandari
authors.forename: Vikhyat S
authors.initials: VS
authors.lastname: Bebarta
authors.forename: Gary A
authors.initials: GA
authors.lastname: Rockwood
authors.forename: Gerry R
authors.initials: GR
authors.lastname: Boss
authors.forename: Brian A
authors.initials: BA
authors.lastname: Logue
mesh_terms: D000818:Animals; D001120:Arginine / Q000097:blood; D003486:Cyanides / Q000097:blood; D006207:Half-Life; D007202:Indicators and Reagents; D007262:Infusions, Intravenous; D007656:Ketoglutaric Acids / Q000493:pharmacokinetics* / Q000633:toxicity*; D009570:Nitriles / Q000493:pharmacokinetics* / Q000633:toxicity*; D010599:Pharmacokinetics; D011042:Poisons / Q000633:toxicity*; D011190:Potassium Cyanide / Q000633:toxicity*; D013552:Swine; D053778:Thiazolidines / Q000097:blood; D013861:Thiocyanates / Q000097:blood
chemical_list: D003486:Cyanides; D007202:Indicators and Reagents; D007656:Ketoglutaric Acids; D009570:Nitriles; D011042:Poisons; D053778:Thiazolidines; D013861:Thiocyanates; C584018:alpha-ketoglutarate cyanohydrin; C430593:cyanohydrin; C020213:arginine thiazolidinecarboxylate; D001120:Arginine; D011190:Potassium Cyanide; C031760:thiocyanate
keywords: Cyanide exposure; Toxicokinetics; α-Ketoglutarate; α-Ketoglutarate cyanohydrin; α-Kg; α-KgCN; α-ketoglutarate; α-ketoglutarate cyanohydrin