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Experimental Biology and Medicine 228:79-83 (2003)
© 2003 Society for Experimental Biology and Medicine

ORIGINAL RESEARCH ARTICLE

Species Comparison of Methemoglobin Reductase

Gary A. Rockwood*,1, Kevin R. Armstrong{dagger} and Steven I. Baskin{ddagger}

* Drug Assessment,
{dagger} Comparative Medicine, and
{ddagger} Pharmacology Divisions, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010–5400

Methemoglobin (MHb) formation is effective in treating cyanide (CN) poisoning. Endogenous activity of the enzyme MHb reductase (MR) reflects the capacity to reduce MHb and thus represents a key factor for evaluating anti-CN efficacy of MHb formers. MR activity was measured in whole blood of nine animal species and was compared with human MR activity. The animals in this comparative study included seven nonhuman primate (NHP) species, the beagle dog, and the ferret. Although exhibiting higher MR activity than in humans, the rhesus and aotus NHPs’ average MR activity was the closest to humans’, with raw data from each NHP showing overlap with human raw data. The beagle dog, used extensively to study anti-CN characteristics of MHb formers, was the sole species that displayed MR activity lower than in humans, with no data overlap. Based on MR activity, the rhesus and aotus NHPs may each represent a more accurate model for predicting human responses to MHb formers. The data from this study provides a unique interspecies enzyme comparison, which should facilitate future rational development of anti-CN MHb formers.

Key Words: methemoglobin reductase • species comparison • nonhuman primates • cyanide • animal models




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