THE ROLE OF HEPATIC DETOXIFICATION IN p-AMINOPROPIOPHENONE INDUCED METHEMOGLOBINEMIA

¹ Biochemistry Section, Medical Division Laboratory, Chemical Warfare Service, Edgewood Arsenal, Md.

In the absence of the liver a single dose of p-aminopropiophenone (PAPP) induces the formation of more methemoglobin than it does in an intact animal. This effect was found to be related to the conjugation of the compound by liver tissue. This conjugation occurs in both man and the rat.

There is a positive correlation between extent of methemoglobinemia and the concentration of free PAPP in the blood.

Free PAPP penetrates freely into the red blood cell, but the conjugated form shows a plasma : cell ratio of about 3:1.

Pretreatment of rats with non-methemoglobin forming aromatic amines (sulfadiazine and p-aminobenzoic acid) results in a higher and more prolonged methemoglobinemia than occurs in normal animals injected with the same dose of PAPP. Rats injected twice daily with PAPP in propylene glycol exhibit a smaller methemoglobinemic response from a single dose of PAPP than do control animals.

Altho PAPP does not induce the formation of methemoglobin in vitro, plasma obtained from PAPP-treated rats does so to an appreciable extent.

The nature of the reaction between PAPP and hemoglobin is discussed in the light of the findings herein reported.