Accession Number : ADP008850

Title :   Marked Differences in Drug-Induced Methemoglobinemia in Sheep are not Due to RBC Glucose-6-Phosphate Dehydrogenase, Reduced Glutathione, or Methemoglobin Reductase Activity.

Corporate Author : ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD

Personal Author(s) : Martin, Dale G. ; Guertler, Andrew T. ; Lagutchik, Michael S. ; Woodard, Claude L., Jr. ; Leonard, Denise A.

Report Date : 13 MAY 1993

Pagination or Media Count : 13

Abstract : Benzocaine is a commonly used topical anesthetic that is structurally similar to current candidates for cyanide prophylaxis. Benzocaine induces profound methemoglobinemia in some sheep but not others. After topical benzocaine administration certain sheep respond to form MHb (elevated MHb 16-50% after a 56-280 mg dose, a 2-10 second spray with benzocine), while other phenotypically similar sheep fail to significantly form MHb (less than a 2% increase from baseline). Deficiencies in Glucose-6-phosphate dehydrogenase (G-6-PD), reduced glutathione (GSH), and MHb reductase increase the susceptibility to methemoglobinemia in man and animals. Sheep are used as a model for G-6-PD deficiency in man, and differences in this enzyme level could cause the variable response seen in these sheep. Similarly, differences in GSH and MHb reductase could be responsible for the observed differences in MHb formation.

Descriptors :   *CYANIDES, ANESTHETICS, DEFICIENCIES, ENZYMES, GLUCOSE, GLUTATHIONE, PHOSPHATE DEHYDROGENASE, PHOSPHATES, SHEEP, SPRAYS, RESPONSE(BIOLOGY).

Subject Categories : Toxicology
      Biochemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE