THE ACTION OF PTEROYL GLUTAMIC ACID AND NATURAL SOURCES OF FOLIC ACID ON BLOOD DYSCRASIAS INDUCED BY SULFONAMIDE DRUGS

Sulfanilamide, sulfathiazole, and sulfadiazine have been fed at 1 per cent levelsin highly purified diets and their effect on growth, mortality, and blood dyscrasiascompared with that of sulfasuxidine.

The soluble drugs produce conditions which are similar to those produced bysulfasuxidine. The growth depression is alleviated in large measure in the case ofsulfanilamide and to a lesser extent for sulfathiazole and sulfadiazine by folic acid.liver extract powder, and dried yeast extract as well as by para-aminobenzoic acid,

The blood dyscrasias due to sulfanilamide, sulfathiazole, and sulfadiazine aresevere leukopenia, granulocytopenia, and mild-to-severe anemia. These are uniformly prevented or the severity greatly curtailed by feeding folic acid, liver extract powder, or dried yeast extract. PABA has a lesser effect in the amounts fed.

Liver extract powder seems to have a beneficial effect on growth and mortalitywhich is not shown by the other supplements. Both free and conjugated folic acid(as yeast extract and in liver extract powder 1:20) are active in combating thedyscrasias.

Evidence from in vitro experiments with Str. haemolyticus (B Lancefield) indicates that neither folic acid, liver extract powder, nor dried yeast extract in ratiosto sulfonamide which are effective in preventing the blood dyscrasias will inhibitor block the bacteriostatic action of the sulfonamide drugs in vitro.

It is suggested that the action of folic acid, liver powder, and yeast extract is notwholly explained by alleviating a folic acid deficiency caused by intestinal bacteriostasis due to the drugs, but by an increased demand of the animals for folicacid in the presence of certain sulfonamides.

Note: We are indebted to Harold Buskirk, Alice Bergdahl, Hallie Ferguson, E. M. Stapert, F. La Plante,and Evon Saggio for valuable assistance in carrying out the experimental work reported here.