FACTORS AFFECTING THE TOXICITY AND METABOLISM OF ORGANIC ARSENICALS (ROXARSONE, COPPER, CYSTEINE).

摘要

Experiments were conducted to examine factors affecting the metabolism and toxicity of the organic arsenical, roxarsone (3-nitro-4-hydroxyphenyl-arsonic acid). In experiments with chicks, cysteine enhanced the toxicity of the organic arsenicals, roxarsone and phenylarsonic acid. However, it had little effect on the toxicity of the inorganic arsenicals As(,2)O(,3) and As(,2)O(,5) or the trivalent form of phenylarsonic acid, i.e., phenylarsine oxide. Supplementation of the diet with cystine, methionine or K(,2)SO(,4) did not exacerbate roxarsone toxicity. Reduced glutathione and ascorbic acid, however, each exacerbated roxarsone toxicity. Therefore the potentiation of toxicity requires pentavalent organic arsenicals and compounds which can act as reducing agents. It was concluded that cysteine exacerbates roxarsone toxicity by reducing it to the more toxic trivalent state.;Both roxarsone and copper had to be present in the diet for the liver copper-lowering effect of roxarsone to be exerted. In addition, feeding roxarsone elevated urinary copper excretion in rats but had no effect on fecal copper excretion. Thus, roxarsone probably binds copper in the gut, forming a roxarsone-copper complex which is then absorbed, but cannot be taken up as such by tissues and subsequently is excreted in the urine.;The effects of roxarsone on weight gain were more perplexing depending on both the species of animal and the level of copper fed. In addition, no interaction was observed between the protozoan parasites Eimeria acervulina or Eimeria tenella and roxarsone.;Roxarsone dramatically reduced tissue copper concentration at all levels of supplemental copper fed to chicks, rats and pigs. Arsanilic acid (4-aminophenylarsonic acid), As(,2)O(,3), As(,2)O(,5) and structural analogs of roxarsone (o-nitrophenol and 3-nitro-4-hydroxybenzoic acid) had no effect on liver copper concentration in birds fed a high level of copper. However, liver cobalt concentration was reduced by the addition of either o-nitrophenol or roxarsone to the diets of birds fed a high level of cobalt. It was concluded that arsenic per se had no effect on liver copper accumulation or depletion but that a chelate was probably formed between copper or cobalt and the nitroso and hydroxyl groups of the ring portion of roxarsone.