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Effect of various antidotes on the biliary and intestinal excretion of arsenic in situ and into the feces in vivo in guinea-pigs after injection of As2O3.

The effect of various antidotes on the excretion of arsenic into the feces in vivo and on the biliary and enteric excretion in situ was investigated on segments of jejunum and colon in anesthetized guinea-pigs using the pendular perfusion technique, according to Henning and Forth (1982). In the in situ experiments guinea-pigs received As2O3 (0.02 mmol As(III)/kg) and 30 min later, British-Anti-Lewisite (BAL), dimercaptopropanesulfonic acid (DMPS), dimercaptosuccinic acid (DMSA) or 2,3-bis-(acetylthio)propanesulfonamide (BAPSA) (0.1 or 0.7 mmol/kg each) into the jugular vein. In the in vivo experiments guinea-pigs received As2O3 s.c. (same dose as above) and 30 min later the same antidotes (0.1 mmol/kg i.p.). The feces were collected for 24 h and the arsenic content measured. During the 60-min perfusion period the amount of arsenic excreted into the jejunum or colon was only 3% or 0.4% of the dose administered, respectively. Of the arsenic dose, 8% was found in the bile. None of the antidotes had an effect on the arsenic excretion into the jejunum or colon. No change in biliary excretion was found in animals treated with BAL, 0.1 or 0.7 mmol/kg, respectively. DMSA, BAPSA or DMPS, 0.1 mmol/kg, increased the biliary excretion of arsenic to 14, 33, or 43% of the dose administered and after 0.7 mmol/kg to 29, 37, or 42%, respectively. Furthermore, a significant increase (P > 0.05) was found for the bile/blood concentration ratio in the following order: control < BAL < DMSA < BAPSA approximately DMPS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Diagnosis and treatment of Wilson's disease.

Wilson's disease (WD) is an autosomal recessive disease that causes increased copper deposition in the liver and basal ganglia with resultant hepatic and neurologic sequelae. In the past few years, dramatic new discoveries have changed our understanding of the pathophysiology of WD. Although there are potentially life-saving therapies for WD, there is much controversy surrounding the optimal treatments of patients in the various stages of the disease. Specifically, the relative roles of penicillamine, trientene, and tetrathiomolybdate in the initial treatment of the symptomatic patient with WD remain to be defined. Zinc monotherapy for maintenance treatment and in the treatment of asymptomatic patients with WD is still controversial. It is also unclear whether neurologic status alone is an indication for liver transplantation in WD. This paper reviews the pathogenesis, genetics, clinical presentation, and diagnosis, with a special emphasis on the treatment controversies that arise in the care of the WD patient.

Chelating Agents↗

Determination and metabolism of dithiol-chelating agents: electrolytic and chemical reduction of oxidized dithiols in urine.

The presence of oxidized species of the dithiol-chelating agents, meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS), in human urine was determined by chemical and electrolytic reduction methods. Urine from a human given either DMSA or DMPS was treated with electrolysis, dithiothreitol, or sodium tetrahydridoborate (NaBH4). The SH groups were derivatized with monobromobimane for the determination of unaltered dithiols. Total dithiol (unaltered and oxidized) was determined by reduction followed by derivatization with monobromobimane. The bimane derivatives were identified and quantified by HPLC and fluorescence. Although all three reduction methods gave similar results, electrolytic reduction of oxidized DMSA and chemical reduction with NaBH4 of oxidized DMPS are recommended based upon both day to day reproducibility and recovery of standards. After reduction a 4-fold increase in DMSA and a 20-fold increase in DMPS were found in urine by 12 h after an oral dose of DMSA or DMPS. These new methods for the determination of dithiols and their oxidized forms should lead to a better understanding of the metabolic properties of these increasingly important orally effective chelating agents.

Borohydrides↗