Mercury clearance from human plasma during in vitro dialysis: screening systems for chelating agents.
Two in vitro systems were evaluated as potential screening methods for determining the most effective chelating agents for use in patients with inorganic mercury poisoning undergoing hemodialysis. The first system consisted of an in vitro clinical hemodialysis unit and the second system consisted of an in vitro equilibrium dialysis procedure. Both systems utilized pooled human plasma. Ten chelating agents were evaluated in these systems to determine their ability to enhance mercury clearance from human plasma. In the absence of chelators, plasma clearance of mercury was negligible. Of the chelating agents tested, 2,3-dimercaptopropanolol, which enhances biliary and fecal excretion of mercury poisoning, and dithiothreitol did not enhance mercury clearance at 90 min in the hemodialysis system. N-acetylcysteine appeared to be the most effective chelating agent of those tested in the hemodialysis system. N-acetylcysteine produced a 73% decrease in perfusate mercury concentration at 90 min. The results of equilibrium dialysis mirrored those of the hemodialysis in that N-acetylcysteine significantly enhanced mercury transfer across the dialysis membrane into the dialysate whereas dithiothreitol did not. If in vivo experiments confirm the present findings, then in vitro dialysis from pooled human plasma either using a standard clinical hemodialyzer or equilibrium dialysis system will be useful screening tools. Our results suggest that equilibrium dialysis may be a convenient and cost effective method to screen potential chelating agents as complementary to hemodialysis for the treatment of inorganic mercury poisoning.
Ferguson
C L
CL
Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Cantilena
L R
LR
D002614:Chelating Agents / Q000378:metabolism*; D003956:Dialysis; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D008627:Mercuric Chloride / Q000493:pharmacokinetics*; D010949:Plasma / Q000378:metabolism*; D006435:Renal Dialysis; D013054:Spectrophotometry, Atomic
D002614:Chelating Agents; D008627:Mercuric Chloride