| Abstrakt: |
It has been demonstrated by several investigators1-7that mono-iodoacetic acid will react with sulfhydryl groups, presumably according to the following equation—RSH + CH2ICOOH → R-S-CH2COOH + HIThat this reaction may have important biological applications is evident from the demonstration that the poisonous effect of iodoacetic acid on the action of the enzyme glyoxalase has been shown2to be due to the removal of the co-ferment, reduced glutathione.8It is also known that some organic arsenicals react with thiol compounds forming condensation products,9and according to the theory of Voegtlin arsenicals exert their toxic effect upon trypanosomes by combining with sulfhydryl groups present in and, in his opinion, essential for the oxygen consumption of these organisms. If the above considerations are correct, it would seem to follow, necessarily, that iodoacetic acid must be toxic to trypanosomes.In vitroexperiments, carried out to test the above conclusion, showed that sodium iodoacetate added to Trypanosoma equiperdum, suspended in the citrated blood of a rat, is in fact very toxic. A 0.001 M solution killed all the organisms as a rule in 2 or 3 minutes. This time naturally varies with the number of trypanosomes in the emulsion and with their resistance. In view of this finding it seemed desirable to test the action of iodoacetate on trypanosomes in vivo.Preliminary experiments with 14 rats showed that the maximum tolerated dose of sodium iodoacetate, injected intravenously into a normal 240 gm. rat, is 0.2 cc. of a 0.25 M solution. 0.3 cc. of this solution kills about 50% of the rats of this weight. These figures are in good agreement with the findings of Hall and Field10on the toxicity of intraperitoneally injected iodoacetate. Subcutaneous and intramuscular injections have also been tried. The toxicity was practically independent of the mode of injection. If rats, which have been infected with Tr. equiperdumand which contain in their blood stream at the time of treatment one trypanosome per 10-15 red blood cells, are injected with doses of 0.2 cc. of a 0.25 M solution, their blood becomes free of trypanosomes, usually in 2-3 hours. Some of the infected rats die from this dose, as a rule, some time after the trypanosomes have disappeared from the blood stream. Thus, it seems that the infected animals are somewhat more sensitive to iodoacetate than normal rats.Summary.1. Sodium monoiodoacetate is highly toxic to Trypanosoma equiperdum.2. The blood stream of rats infected with trypan-osomes can be freed from these organisms by the intravenous injection of tolerated doses of sodium iodoacetate. The blood remains free for a period varying from 2 to 10 days after which trypano-somes reappear. The treatment may be repeated. 3. The toxic action of iodoacetate upon either rats or trypanosomes could not be counteracted by a 20-fold excess of thiol compounds. 4. Arsenic resistant strains of trypanosomes are not resistant to iodoacetate. 5. The mechanism of the action of iodoacetate is discussed. |
