Enhanced bismuth digestive absorption in rats by some sulfhydryl compounds: nmr study of complexes formed

In a preliminary paper [Thérapie 34, 397 (1979), we showed that cysteine enhances bismuth digestive absorption in rats. In this paper, we have studied in rats the effects of various thiol compounds (mercaptopropionic acid, penicillamine, cysteine, homocysteine, 2-mercaptoethylamine, mercaptoethane) and nonthiol compounds (methionine, serine, alanine) orally administered on the absorption and elimination of bismuth also given orally. Bismuth was measured in blood and urine by electrothermal atomic absorption spectrophotometry. All of the thiol substances, and particularly cysteine, homocysteine, and mercaptopropionic acid, have considerably enhanced bismuth absorption and elimination; whereas, nonthiol substances have had no effect. Moreover, the acute toxicity of bismuth was enhanced when bismuth was given as a complex with cysteine (LD50 = 156 +/- 20 mg/kg). Studies by nmr spectroscopy of interactions between bismuth and these organic compounds have shown that bismuth induces an important chemical shift of the protons of the alpha carbon of the sulfhydrile group. Mainly, studies of C and N have confirmed this fact. The selectivity of such a complexation, in our pH conditions, may be tentatively explained on the ground of hard and soft acid and base (HSAB) theory. We have suggested that an increase in the concentration of thiol compounds in the gastrointestinal tract arising from food, or more probably from microorganism synthesis, could be an explanation for human encephalopathies.