Interactions between selenium and group Va-metalloids (arsenic, antimony and bismuth) in the biliary excretion.

The interrelationship between the biliary excretion of exogenous group Va-metalloids (arsenic, antimony and bismuth) and selenium, as well as endogenous glutathione has been studied in rats injected intravenously with sodium selenite and one of the group Va-metalloids. Arsenic, antimony and bismuth appeared in the bile of rats together with large amounts of non-protein thiols (NPSH, representing glutathione and its SH-containing degradation products) and, with the exception of bismuth, they caused choleresis. Significant interactions were observed in the hepatobiliary disposition between selenium and each of the group Va-metalloids, however, their outcomes were not uniform. When coadministered with sodium arsenite or arsenate, selenite enhanced the initial biliary excretion of arsenic 2- and 8-fold, respectively, without further increasing the concomitant excretion of NPSH or the choleretic effect of arsenicals. However, selenite augmented neither the excretion of antimony or bismuth, nor the simultaneous biliary release of NPSH. In turn, arsenite, arsenate and antimony potassium tartrate increased the initial biliary excretion of selenium more than 10-fold and enhanced the accumulation of selenium in blood (exclusively in the erythrocytes). In contrast, administration of bismuth ammonium citrate diminished both the biliary excretion and the erythrocytic accumulation of selenium, while causing retention of selenium in the blood plasma. In rats receiving arsenic or antimony with selenite, the time courses of the biliary excretion of these group Va-metalloids, selenium and NPSH were similar. It is hypothesised that incorporation of selenol metabolites of selenite into the glutathione complexes of arsenic and antimony, resulting in cholephilic ternary complexes, accounts for the arsenic- and antimony-induced augmentation of the hepatobiliary transport of selenium. However, additional chemical and/or dispositional mechanisms are thought to be responsible for the selenite-induced increase in biliary excretion of arsenic.

Increased biliary excretion of glutathione is generated by the glutathione-dependent hepatobiliary transport of antimony and bismuth.

We have recently demonstrated that the hepatobiliary transport of arsenic is glutathione-dependent and is associated with a profound increase in biliary excretion of glutathione (GSH), hepatic GSH depletion and diminished GSH conjugation (Gyurasics A, Varga F and Gregus Z, Biochem Pharmacol 41: 937-944 and Gyurasics A, Varga F and Gregus Z, Biochem Pharmacol 42: 465-468, 1991). The present studies in rats aimed to determine whether antimony and bismuth, other metalloids in group Va of the periodic table, also possess similar properties. Antimony potassium tartrate (25-100 mumol/kg, i.v.) and bismuth ammonium citrate (50-200 mumol/kg, i.v.) increased up to 50- and 4-fold, respectively, the biliary excretion of non-protein thiols (NPSH). This resulted mainly from increased hepatobiliary transport of GSH as suggested by a close parallelism in the biliary excretion of NPSH and GSH after antimony or bismuth administration. Within 2 hr, rats excreted into bile 55 and 3% of the dose of antimony (50 mumol/kg, i.v.) and bismuth (150 mumol/kg, i.v.), respectively. The time courses of the biliary excretion of these metalloids and NPSH or GSH were strikingly similar suggesting co-ordinate hepatobiliary transport of the metalloids and GSH. However, at the peak of their excretion, each molecule of antimony or bismuth resulted in a co-transport of approximately three molecules of GSH. Diethyl maleate, indocyanine green and sulfobromophthalein (BSP), which decreased biliary excretion of GSH, significantly diminished excretion of antimony and bismuth into bile indicating that hepatobiliary transport of these metalloids is GSH-dependent. Administration of antimony, but not bismuth, decreased hepatic GSH level by 30% and reduced the GSH conjugation and biliary excretion of BSP. These studies demonstrate that the hepatobiliary transport of trivalent antimony and bismuth is GSH-dependent similarly to the hepatobiliary transport of trivalent arsenic. Proportionally to their biliary excretion rates, these metalloids generate increased biliary excretion of GSH probably because they are transported from liver to bile as unstable GSH complexes. The significant loss of hepatic GSH into bile as induced by arsenic or antimony may compromise conjugation of xenobiotics with GSH.

Saturable, sodium-induced release of potassium in the muscle exposed to glycerol.

Investigating the kinetics of K+ efflux, two K+ fractions were found in the muscle exposed to 5.8 M glycerol solution at -12 degrees C. The minor K+ fraction was exchangeable with Na+. The amount of released K+ ions being in the K+/Na+ ion exchange was saturable with increase in the concentration of Na+ ion in the medium. It was 11 mmol K+/kg wet wt., which corresponds to the magnitude of the "medium" K+ fraction found by A. S. Troshin in the muscle by means of isotope technique. The minor K+ fraction was temperature and ouabain dependent. K+ fraction with similar features was found by W. Negendank in human lymphocytes, however, its magnitude was 120 mmol K+/kg w.wt. The ratio of the two magnitudes is equal to the ratio of the total cell surface of the muscle and the lymphocyte of one kg. From this fact, it can be concluded that the 11 mmol K+/kg fraction exchangeable with Na+ is bound directly to the cell membrane or to an unidentified structure near to the membrane surface. The preference of K+ binding at higher temperature is interpreted by the assumption that both K+ and Na+ bind to the binding sites of the 11 mmol/kg fraction with their hydration shells.

Investigation of hydration of macromolecules. III. Study of polyethylene glycol homologues by microwave measurements.

The microwave conductivity and permittivity of various homologues of polyethylene glycol (PEG), as well as those of dioxane, all dissolved in either water or electrolyte solutions containing 0.01 M MnSO4, were measured over the frequency range of 1.5 to 4.2 GHz, at a temperature of 30 degrees C. The conductivity was also determined at the frequency of 20 kHz, at the same temperature. We found that: The wavelength of the dielectric relaxation of water increased with the increase of the concentration of nonelectrolytes. The orientation polarization of PEG molecules with a degree of polymerization of n less than or equal to 12.5 can be detected over the microwave range studied. In solution of PEG macromolecules at a degree of polymerization n greater than 12.5 the microviscosity and the wavelength of dielectric relaxation of water significantly increase because of the cooperative action of regularly ordered hydrophilic groups. The ionic conductivity is inversely proportional to the microviscosity of the water. There is a constant conductivity over the microwave range studied, presumably due to the orientational polarization of water molecules interacting with the macromolecules (relaxation frequency f congruent to 0.25 to 0.5 GHz). The effect of PEG of a high polimerization degree on the structure of water is similar to the effect of a decreasing temperature.