Effects of P-aminopropiophenone (PAPP), P-aminoheptanoylphenone (PAHP), and P-aminooctanoylphenone (PAOP) Exposure on Methemoglobin, Sulfhemoglobin, Oxyhemoglobin, Oxygen Content, Reduced Hemoglobin, Oxygen Saturation, Carboxyhemoglobin, and Oxygen Capaci

摘要

Methemoglobin (MHb) formation is one strategy to counter cyanide (CN) toxicity.Currently available MHb formers present certain drawbacks and limitations. The purpose of this study was to characterize, in mice, the hematologic effects of the MHb-forming compound p-aminopropiophenone (PAPP), and two structurally related phenones, p-aminoheptanoylphenone (PAHP) and p-aminooctanoylphenone (PAOP). Although these three phenones have been shown previously to be efficacious against CN, a more complete understanding of their hematologic effects is lacking. Using a hemoximeter, blood samples were obtained -2 to +180 min relative to intramuscular (im) or intraperitoneal (ip) injections. Sodium nitrite (NaNO2) and the appropriate solvents served as the positive and negative controls, respectively. Dose, time, route, and compound-related effects were observed. MHb and sulfhemoglobin levels tended to increase, whereas levels of those parameters related to oxygen carrying capacity of the blood, such as oxygen content, oxygen saturation, oxyhemoglobin and reduced hemoglobin were reduced. Small reductions or no measurable changes were observed in carooxyhemoglobin and oxygen capacity. In general, the effects of PAHP and PAOP tended to be longer lasting than those observed with PAPP and NaNO2. Furthermore, PAPP and NaNO2 were equally effective im or ip, whereas PAHP and PAOP showed larger effects when administered ip. Although additional work is needed, these data provide information which will be useful for the successful development of improved anti-CN MHb formers.