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 f eces in vivo and on the biliary and enteric excretion in situ was inve stigated 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 AS(2)O(3) (0. 02 mmol As(III)/kg) and 30 min later, British-Anti-Lewisite (BAL), dim ercaptopropanesulfonic acid (DMPS), dimercaptosuccinic acid (DMSA) or 2,3-bis-(acetylthio)propanesulfonamide (BAPSA) (0.1 or 0.7 mmol/kg eac h) into the jugular vein. In the in vivo experiments guinea-pigs recei ved As2O3 s.c. (same dose as above) and 30 min later the same antidote s (0.1 mmol/kg i.p.). The feces were collected for 24 h and the arseni c content measured. During the 60-min perfusion period the amount of a rsenic excreted into the jejunum or colon was only 3% or 0.4% of the d ose administered, respectively. Of the arsenic dose, 8% was found in t he 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, BAP SA 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 > 0.0 5) was found for the bile/blood concentration ratio in the following o rder: control <BAL<DMSA<BAPSA approximate to DMPS. In the in vivo expe riments the amount of feces excreted did not differ between groups. Du ring 24 h the cumulative arsenic excretion with the feces was 3.4 +/- 0.8% of the dose administered (mean +/- SEM). No change was observed a fter antidote application. In addition to the results in the in situ e xperiments, the results indicate enterohepatic recycling of arsenic an d/or the arsenic antidote compounds in guinea-pigs.