Pharmacodynamic study of the selenium-mediated arsenic excretion in arsenicosis patients in Bangladesh

摘要

Since 1938 several investigators have confirmed antagonistic interaction whereby the adminis-tration of selenite mitigates arsenite toxicity in mammals.More recently a number of animal model and human studies have revealed that the bimolecular basis of this antagonism involves the glutathione mediated formation of major metabolite seleno-bis(S-glutathionyI)arsinium [(GS)2AsSe]-ion which is rapidly excreted through bile.To investigate whether the oral supplementation of sodium selenite will enhance the fecal excretion of arsenites in human,a limited pharmacodynamics study was carried out involving ten arsenicosis patients.However,data from five patients are reported here.Patients were screened for pre-existing hepatic diseases and they were excluded from the study.Subjects were selected based on the arsenic level in their household drinking water,hair,nail samples and diffuse melanosis symptoms.Patients received ~(77)Se-labeled sodium selenite as oral supple-ment,which they ingested together with their arsenic-containing drinking water.Total selenium levels increased in both urine and feces following the co-administration of sodium selenite (800 μg).The patients receiving a placebo showed no change in their selenium excretion.The increase in selenium levels in feces and arsenic to some extent after dosing agrees with our hypothesis that selenium supplementation promotes co-excretion of arsenic and selenium through formation of [(GS)2AsSe]-in the bile.