Redox activities of mercury-thiol complexes: implications for mercury-induced porphyria and toxicity.
Mercury exposure causes oxidative damage to the kidney, resulting in numerous biochemical changes, including the excretion of excess porphyrins in the urine (porphyrinuria). Hg(II)-induced porphyrinuria may occur, in part, by the previously reported oxidation of reduced porphyrins (porphyrinogens) by a GSH/Hg(II) complex and H2O2. To further elucidate the mechanism(s) of porphyrinogen oxidation by GSH, Hg(II), and H2O2, we compared the ability of several thiol compounds and peroxides to substitute for GSH or H2O2, respectively, in the oxidation of uroporphyrinogen (urogen). Every thiol compound tested resulted in enhanced urogen oxidation in the presence of Hg(II) and H2O2, albeit at different rates. Additionally, t-butyl or cumene hydroperoxide substituted for H2O2 in promoting urogen oxidation, although neither peroxide was as effective in this regard. Mercury-thiol complexes synthesized from Hg(I) and GSSG also promoted urogen oxidation in the presence of H2O2. Additionally, in the absence of urogen, both GSH/Hg(II) or GSSG/Hg(I) catalyzed the decomposition of H2O2. Finally, incubation of GSH/Hg(II) or GSSG/Hg(I) with H2O2 resulted in HPLC-detectable products distinct from GSH, GSSG, or GS2Hg(II). These findings suggest that mercury-thiol complexes possess redox activity in biological systems, which promotes the oxidation of porphyrinogens and possibly other biomolecules.
Miller
D M
DM
Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle 98195.
Woods
J S
JS
D004347:Drug Interactions; D005978:Glutathione / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008628:Mercury / Q000633:toxicity*; D010084:Oxidation-Reduction / Q000187:drug effects; D011164:Porphyrias / Q000139:chemically induced*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014577:Uroporphyrinogens / Q000378:metabolism; D014578:Uroporphyrins / Q000378:metabolism
D013438:Sulfhydryl Compounds; D014577:Uroporphyrinogens; D014578:Uroporphyrins; D006861:Hydrogen Peroxide; D008628:Mercury; D005978:Glutathione