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)
Reichl
F X
FX
Walther Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, Germany.
Kreppel
H
H
Szinicz
L
L
Mückter
H
H
Fichtl
B
B
Forth
W
W
D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001151:Arsenic / Q000097:blood / Q000378:metabolism*; D020261:Arsenic Poisoning; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004112:Dimercaprol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005243:Feces / Q000737:chemistry; D006168:Guinea Pigs; D007275:Injections, Intravenous; D007583:Jejunum / Q000187:drug effects*; D008297:Male; D010087:Oxides / Q000008:administration & dosage / Q000633:toxicity*; D010477:Perfusion; D011041:Poisoning / Q000188:drug therapy; D004113:Succimer / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014494:Unithiol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000931:Antidotes; D001152:Arsenicals; D010087:Oxides; D013449:Sulfonamides; D004112:Dimercaprol; C093085:2,3-bis(acetylthio)propanesulfonamide; D014494:Unithiol; D004113:Succimer; D001151:Arsenic; D000077237:Arsenic Trioxide