XII. DETOXICATION OF ARSENICALS 65 



inhibit the thjToid, thus decreasing tissue metabolism and, concomitantly, 

 arsenoxide formation. 



It has been mentioned that PABA does not influence the lethal action 

 of the more usual type of arsenicals such as mapharside, neoarsphenamine, 

 etc. In contrast to this, the trypanocidal action of 7-(p-arsenosophenyl)- 

 butyric acid is completely inhibited by the vitamin. Williamson and 

 Lourie^'- '^ demonstrated this interference both in vivo and in vitro. The 

 authors noted that lethal quantities of arsenic are absorbed by trypano- 

 some cells in a matter of seconds. Furthermore, the arsenical, when in- 

 jected, disappears from the blood stream in one-half hour, with or without 

 the prior administration of PABA. The rapidity with which the arsenical 

 takes effect is believed responsible for the inability of PABA to interfere 

 in the "cidal" activity when the vitamin is administered subsequently to 

 the arsenical. 



In vitro, PABA immobilizes Trypanosoma rhodesiense reversibly and 

 innocuously and protects the organism for at least 24 hours from the ac- 

 tion of 7-(p-arsenosophenyl)but3^ric acid. Williamson and Lourie express 

 the opinion that PABA immobilizes the parasite cell by absorption into, 

 or adsorption on the surface of, the organism. Presumably, this process 

 inhibits the lethal action of the arsenical by impeding its penetration into 

 the cell or its fixation on the surface of the cell. 



The inhibition of the trypanocidal activity of 7-(p-arsenosophenyl)- 

 Inityric acid by PABA, a property which this vitamin does not exercise 

 against the usual arsenicals, is attributed by Williamson and Ijourie to the 

 different process by which this arsenical permeates the cell. In support of 

 this view the authors cite the activity of this compound against trypars- 

 amide-resistant strains of the trj'panosome, as well as the presence of the 

 acetic acid configuration, a structure which has been found to be common 

 to the group of arsenicals active against atoxyl-resistant trypanosomes. 

 These compounds are rendered more water-soluble by the presence of the 

 more polar groups and would be expected to penetrate the cell in a fashion 

 different from that of compounds devoid of hydrophilic groups. The latter 

 type of arsenical ostensibly enters via the lipid components of the organism. 



It has been mentioned that except for its anomalous behavior in the 

 case of 7- (p-arsenosophenyl) butyric acid PABA does not reduce the tryp- 

 anocidal action of any of the arsenicals. Schleyer and Schnitzer'^ have 

 found, however, that the methyl and ethyl esters and the amides of benzoic, 

 p-hydroxybonzoic, 7?-aminoV)enzoic, 2,4- and 2,5-dihydroxybenzoic, and 

 nicotinic acid do reduce the jiarasiticidal activity of mapharside or acriflavin 



'3 J. Williamson and E. M. Lourie, Ann. Trop. Med. Parasitol. 40, 255 (1946). 



'^ J. Williamson and E. M. Lourie, Nature 161, 103 (1948). 



15 W. L. Schleyer and R. J. Schnitzer, ./. Immunol. 60, 265 (1948). 



