Reduction of liver copper concentration by the organic arsenical, 3-nitro-4-hydroxyphenylarsonic acid.

The interaction between 3-nitro-4-hydroxyphenylarsonic acid (roxarsone) and Cu was studied in a series of experiments with crossbred, broiler-type chicks. A fully fortified corn-soybean meal diet was fed in all assays. While roxarsone caused a marked reduction in liver Cu concentration, arsanilic acid (4-aminophenylarsonic acid), As2O3 and As2O5 were without effect. When structural analogs of roxarsone were studied, it was found that o-nitrophenol and 3-nitro-4-hydroxybenzoic acid also had no effect on liver Cu concentration in birds fed a high level of Cu. However, liver Co concentration was reduced by the addition of either o-nitrophenol or roxarsone to the diets of birds fed a high level of Co. It was concluded that arsenic per se had no effect on liver Cu accumulation or depletion, but that a chelate was probably formed between Cu or Co and the nitroso and hydroxyl groups of the ring portion of roxarsone. In addition to the reduction in liver Cu deposition, concentrations of Cu in the bile, brain, heart and pancreas of chicks were reduced by the addition of roxarsone to a high-Cu diet. Neither dietary nor intraperitoneally (ip) injected roxarsone had an effect on liver Cu concentration when Cu was injected ip. Therefore, both roxarsone and Cu had to be present in the diet for the liver Cu-lowering effect of roxarsone to be exerted. A further experiment was conducted with growing rats to determine the effect of roxarsone on Cu balance. Feeding roxarsone elevated Cu excretion in the urine but had no effect on Cu excretion in the feces.