Relationships between the renal handling of DMPS and DMSA and the renal handling of mercury.
Within the body of this review, we provide updates on the mechanisms involved in the renal handling mercury (Hg) and the vicinal dithiol complexing/chelating agents, 2,3-bis(sulfanyl)propane-1-sulfonate (known formerly as 2,3-dimercaptopropane-1-sulfonate, DMPS) and meso-2,3-bis(sulfanyl)succinate (known formerly as meso-2,3-dimercaptosuccinate, DMSA), with a focus on the therapeutic effects of these dithiols following exposure to different chemical forms of Hg. We begin by reviewing briefly some of the chemical properties of Hg, with an emphasis on the high bonding affinity between mercuric ions and reduced sulfur atoms, principally those contained in protein and nonprotein thiols. A discussion is provided on the current body of knowledge pertaining to the handling of various mercuric species within the kidneys, focusing on the primary cellular targets that take up and are affected adversely by these species of Hg, namely, proximal tubular epithelial cells. Subsequently, we provide a brief update on the current knowledge on the handling of DMPS and DMSA in the kidneys. In particular, parallels are drawn between the mechanisms participating in the uptake of various thiol S-conjugates of Hg in proximal tubular cells and mechanisms by which DMPS and DMSA gain entry into these target epithelial cells. Finally, we discuss factors that permit DMPS and DMSA to bind intracellular mercuric ions and mechanisms transporting DMPS and DMSA S-conjugates of Hg out of proximal tubular epithelial cells into the luminal compartment of the nephron, and promoting urinary excretion.
Division of Basic Medical Sciences, 1550 College Street, Mercer University School of Medicine, Macon, GA 31207, USA. zalups_rk@mercer.edu
Rudolfs K
RK
Zalups
Christy C
CC
Bridges
D000818:Animals; D002614:Chelating Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D029382:Dicarboxylic Acid Transporters / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D008628:Mercury / Q000737:chemistry* / Q000378:metabolism / Q000652:urine; D008630:Mercury Poisoning / Q000188:drug therapy; D027361:Organic Anion Transporters / Q000378:metabolism; D004113:Succimer / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014494:Unithiol / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D002614:Chelating Agents; D029382:Dicarboxylic Acid Transporters; D027361:Organic Anion Transporters; D013438:Sulfhydryl Compounds; D014494:Unithiol; D004113:Succimer; D005723:gamma-Glutamyltransferase; D008628:Mercury