Effect of DMPS and various adsorbents on the arsenic excretion in guinea-pigs after injection with As2O3.
The present experiments were performed to test the possibility of interrupting the enterohepatic circulation of arsenic (As). Therefore the efficacy of adsorbents to bind As and/or As-DMPS adducts in vitro and their effect on the excretion of As into the feces and urine in vivo were investigated after injection of As2O3 and DMPS in guinea-pigs. The adsorbents bentonite, activated charcoal or colestyramine, respectively, were tested. Only slight binding of 73As (< 5% of the 73As dose) was observed to all adsorbents in vitro. After addition of DMPS, a good binding was found for 73As to colestyramine (50%) or activated charcoal (60%), respectively. However, the 73As-DMPS adduct was removed from the activated charcoal during washing. In the first in vivo experiment, male guinea-pigs (n = 4/group) received As2O3 [0.02 mmol As(III)/kg s.c. labelled with a tracer dose of 73As(III) (0.14 kBq/g)], 30 min later DMPS (0.1 mmol/kg i.p.) and by gastric tube (10 ml/kg body wt) either saline, bentonite (1 g/kg), activated charcoal (1 g/kg) or colestyramine (0.2 g/kg), respectively. Urine and feces were collected for 24 h. No increase in 73As excretion into the feces was observed after administration of DMPS and all adsorbents, compared to control animals. In the second in vivo experiment male guinea-pigs (n = 4/group) received the same As2O3 (+ 73As)- and DMPS dose. In addition, with a gastric tube (10 ml/kg) saline, colestyramine (0.2 g/kg), DMPS (0.1 mmol/kg), or the combination of DMPS (0.1 mmol/kg) + colestyramine (0.2 g/kg) were administered according to the scheme given in the following table. The amount of feces excreted did not differ between groups. Excretion of 73As within the feces during the first 12 h after As injection is shown in the following table (mean +/- SEM). The same amount of 73As (34% of the 73As dose) was excreted into the urine from animals in groups 4 and 5 during this time. Obviously, the combined oral administration of DMPS + colestyramine markedly enhanced fecal excretion of As mobilized by DMPS i.p. It is suggested that interruption of enterohepatic circulation of As may be a valuable adjunct in the treatment of As poisoning.
Reichl
F X
FX
Walther-Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, Germany.
Hunder
G
G
Liebl
B
B
Fichtl
B
B
Forth
W
W
D000818:Animals; D000837:Anion Exchange Resins / Q000494:pharmacology; D000931:Antidotes / Q000494:pharmacology*; D001151:Arsenic / Q000032:analysis / Q000378:metabolism* / Q000652:urine; D020261:Arsenic Poisoning; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D001546:Bentonite / Q000494:pharmacology; D002606:Charcoal / Q000494:pharmacology; D002792:Cholestyramine Resin / Q000494:pharmacology; D005243:Feces / Q000737:chemistry; D006168:Guinea Pigs; D007279:Injections, Subcutaneous; D008297:Male; D010087:Oxides / Q000008:administration & dosage / Q000633:toxicity*; D014494:Unithiol / Q000494:pharmacology*
D000837:Anion Exchange Resins; D000931:Antidotes; D001152:Arsenicals; D010087:Oxides; D002792:Cholestyramine Resin; D001546:Bentonite; D002606:Charcoal; D014494:Unithiol; D001151:Arsenic; D000077237:Arsenic Trioxide