REDOX ACTIVITIES OF MERCURY-THIOL COMPLEXES - IMPLICATIONS FOR MERCURY-INDUCED PORPHYRIA AND TOXICITY

Mercury exposure causes oxidative damage to the kidney, resulting in n umerous biochemical changes, including the excretion of excess porphyr ins in the urine (porphyrinuria). Hg(II)-induced porphyrinuria may occ ur, in part, by the previously reported oxidation of reduced porphyrin s (porphyrinogens) by a GSH/Hg(II) complex and H2O2. To further elucid ate the mechanism(s) of porphyrinogen oxidation by GSH, Hg(II), and H2 O2, we compared the ability of several thiol compounds and peroxides t o substitute for GSH or H2O2, respectively, in the oxidation of uropor phyrinogen (urogen). Every thiol compound tested resulted in enhanced urogen oxidation in the presence of Hg(II) and H2O2, albeit at differe nt rates. Additionally, t-butyl or cumene hydroperoxide substituted fo r 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. A dditionally, in the absence of urogen, both GSH/Hg(II) or GSSG/Hg(I) c atalyzed 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-thio l complexes possess redox activity in biological systems, which promot es the oxidation of porphyrinogens and possibly other biomolecules.