An extracorporeal complexing hemodialysis system for the treatment of methylmercury poisoning.  I.  In vitro studies of the effects of four complexing agents on the distribution and dialyzability of methylmercury in human blood.
Almost all of the methylmercury (MM) in human blood is protein bound, primarily to sulfhydryl ligands.  Sulfhydryl agents such as penicillamine, N-acetylpenicillamine, cysteine and N-acetyleysteine are capable of reversing the protein binding of MM when they are added to whole human blood.  The magnitude of the protein binding reversal was similar for each compound as predicted by the determination of their relative affinities for MM in vitro.  Concentration-dependent reversals of protein binding of MM in blood was observed at increasing sulfhydryl concentrations from 10-4 to 10-2 M.  At 10-2 M, a 55- to 60-fold increase in non-protein-bound plasma MM was observed, when compared to blood with no added sulfhydryl agent.  Both the complexing agent and the MM complex formed in blood were readily dialyzable using a Travenol 145 twin coil hemodialyzer.  At cysteine concentrations of 10-2 M in whole blood, up to 44 percent of whole blood MM was dialyzed on a single pass at a dialyzer blood flow rate of 55 ml/min.  Under the same conditions, up 50 94 percent of plasma cysteine was dialyzed.  A system is presented for use in vivo on experimental animals.  The potential advantages of this method over existing therapeutic regimens for MM poisoning are discussed.
D000085:Acetates / Q000494:pharmacology; D000111:Acetylcysteine / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008629:Mercury Isotopes; D008630:Mercury Poisoning / Q000628:therapy*; D008767:Methylmercury Compounds / Q000097:blood / Q000506:poisoning*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011868:Radioisotopes; D006435:Renal Dialysis; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D013997:Time Factors
D000085:Acetates; D001798:Blood Proteins; D008629:Mercury Isotopes; D008767:Methylmercury Compounds; D011868:Radioisotopes; D013439:Sulfhydryl Reagents; D010396:Penicillamine; D003545:Cysteine; D000111:Acetylcysteine