Accession Number : ADA182208

Title :   Effectiveness and Mechanisms of Antagonism of Toxic Effects of Cyanide by Alpha-Keto Acids.

Descriptive Note : Final rept. 15 Sep 85-14 Sep 86,

Corporate Author : MISSISSIPPI UNIV MEDICAL CENTER JACKSON DEPT OF PHARMACOLOGY AND TOXICOLOGY

Personal Author(s) : Hume,Arthur S

PDF Url : ADA182208

Report Date : 31 Dec 1986

Pagination or Media Count : 33

Abstract : The purpose of this project has been to investigate the development of an antidotal and/or prophylactic agent to antagonize the toxic effects of cyanide (CN). The work centered around carbonyl containing chemicals - alpha-keto acids. Alpha-ketobutyric (alpha-KB), glutamic, alpha-ketoglutaric (alpha-KG), B-ketoglutaric (B-KG), dehydroascorbic and pyruvic (PRY) acids were studied. Alpha-Ketoacids were shown to bind cyanide in vitro. Evidence of this binding is the decreased concentration of alpha-keto acids and the decreased quantities of cyanide released from mixtures of potassium cyanide and alpha-keto acids both prophylactically and antidotally by intraperitoneal administration. Alpha-KG showed the least toxicity (up to 4.0 grams/kg) although other keto acids were slightly more effective as antidotes. Studies into the mechanism have been done, alpha-KG does prevent the inhibition of cytochrome oxidase by cyanide and has no effect on the transulfurase, rhodanese. Alpha-KG does not enhance the formation of methemoglobin or thiocyanate. In studies involving the dogs, nine cardiovascular and thirteen blood gas parameters were measured and evaluated for the antagonistic effects of alph-KG on cyanide toxicity. From these studies, alpha-KG is effective in antagonizing administered dose of CN of five times the lethal dose before the toxic effects are irreversible.

Descriptors :   *CYANIDES, *TOXICITY, *ANTIDOTES, *KETONES, *ORGANIC ACIDS, *PHARMACOLOGICAL ANTAGONISTS, BLOOD GASES, INHIBITION, IN VITRO ANALYSIS, CYTOCHROME OXIDASE, METHEMOGLOBIN, LETHAL DOSAGE, ASCORBIC ACID, BUTYRIC ACIDS, GLUTAMIC ACID, GLUTARIC ACID, PYRUVIC ACID, QUANTITY, MIXTURES, POTASSIUM, PREVENTIVE MEDICINE, THIOCYANATES

Subject Categories : Medicine and Medical Research
      Toxicology
      Biochemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE