Toxic Action of Hydrogen Peroxide on Trypanosomes and a Note on Chemotherapeutic Mechanism

Abstract

We previously described 1 the toxic action of auto-oxidized ami-nophenol and of quinone upon trypanosomes and ascribed the action of aminophenols to the formation of quinoid compounds. However, another possible mechanism seemed worthy of consideration. During oxidation processes by molecular oxygen (auto-oxidation) intermediary peroxides are formed which readily hydrolyze in the presence of water forming H₂O₂.∗ Both the organic peroxides and the hydrogen peroxide may have a toxic action on trypanosomes. The nature of the supposed organic peroxide concerned in amino-phenol oxidation is unknown, hence this could not be studied, but it was relatively easy to study the toxic action of H₂O₂ on trypanosomes.

We found that trypanosomes, Tr. equiperdum, suspended in Locke solution containing 0.5% glucose were immobilized almost immediately when the added H₂O₂ reached the concentration of 1/30,000. A trypanosome emulsion obtained in the manner outlined in the previous paper was prepared. A solution of hydrogen peroxide was made by diluting 0.1 cc. of Merck's 30% H₂O₂ to-100 cc. with 0.85% NaCl solution. A mixture was made containing 0.6 cc. of the Locke solution, 0.1 cc. of the H₂O₂ solution and 0.1 cc. of 0.85% NaCl solution with 0.2 cc. of the trypanosome emulsion. After 5 minutes no motility was observed. After 10 minutes 0.2 cc. of the fresh rabbit plasma was added and 5 minutes after this slight motility was seen. The addition of catalase or of fresh serum inhibits this toxicity to a certain extent. It was also found that trypanosomes obviously damaged by H₂O₂ will recover after the addition of fresh serum, the catalase content of which decomposes the H₂O₂. Since trypanosomes themselves contain catalase, the action of hydrogen peroxide naturally depends also on the density of trypanosomes present in the emulsion.