The Detoxifying Action of Vitamin C (Ascorbic Acid) in Arsenical Therapy

Abstract

The reduction of the toxic side effects of chemotherapeutic drugs is one of the major problems of chemotherapy. During the first period of the development of chemotherapy every effort was made to modify the chemical constitution of the products synthesized in order to increase their parasitotropic properties and to reduce their organotropic affinities.More recently it was found that the toxicity of some well established chemotherapeutic agents may be reduced by giving simultaneously certain other substances which produce a detoxifying effect. Ehrlich,1 in one of his earliest papers on chemotherapy, pointed out that "reduction" is the most important chemical reaction in the detoxifying process of chemotherapeutic agents, especially the arsphenamines.Among the various substances recommended and applied as detoxifying agents, vitamin C (1-ascorbic acid) stands in a unique position. While most of the other substances are products foreign to the body, ascorbic acid is one of the most powerful physiologic reducing agents.Animals that are able to synthesize ascorbic acid, such as the rat, respond with an increased formation of this substance to toxic doses of a great number of drugs.2 Man is not able to synthesize it. In man, the vitamin C for detoxification must come either from the ingested food or from the body stores. Syphilitic patients when, given neoarsphenamine in therapeutic doses had a more or less decided decline of their plasma ascorbic acid levels.3 The drop in the plasma ascorbic acid was especially pronounced in patients who showed symptoms of intolerance to arsenicals.The influence of ascorbic acid on the sensitization of guinea pigs to arsphenamine was first reported by Sulzberger and Oser.4 In 1937 ascorbic acid was rec¬ ommended for the detoxification of arsphenamines in human therapy by Dainow.5 Since his publication other reportse have appeared confirming Dainow's 7 obser¬ vations, but a number of authors 8 have not obtained as favorable results.For more than a year we have attempted to desensi¬ tize patients hypersensitive to arsenical drugs by build¬ ing up and maintaining their plasma ascorbic acid level at an optimal range.9 In the course of this clinical and biochemical study some observations were made proving that ascorbic acid definitely counteracts the toxic action of neoarsphenamine and mapharsen in man.It is well known that solutions of arsphenamine become oxidized if they are exposed to air and that such oxidized solutions are much more likely to cause toxic side effects than freshly prepared solutions of the same drug.In experiments on mice Dainow 5 showed that the injection of a freshly prepared solution of arsphenamine killed 35 per cent of the animals. When the same solution was allowed to stand for from three to five hours, its toxicity increased to such a degree that when injected in the same amounts 70 per cent of the mice were killed. However, when ascorbic acid was added to the freshly prepared solution, its toxicity did not increase. On the contrary, it was lower than the toxi...