Does mercury promote lipid peroxidation? An in vitro study concerning mercury, copper, and iron in peroxidation of low-density lipoprotein.
In order to explore the observed association among mercury, atherosclerosis, and coronary heart disease, the effects of mercury, copper, and iron on the peroxidation of low-density lipoprotein (LDL) and on the enzymatic activities of glutathione peroxidase and myeloperoxidase were investigated in vitro. On the basis of our nuclear magnetic resonance (NMR) experiments, we conclude that mercury does not promote the direct nonenzymatic peroxidation of LDL, like copper and iron. In our enzyme measurements, mercury inhibited slightly myeloperoxidase, although not significantly in presence of LDL. Instead, inorganic mercury, but not methylmercury chloride, inhibited glutathione peroxidase effectively and copper even at 10 micromol/L, below physiological concentrations, doubled the inhibition rate. Copper and iron had no direct effect on glutathione peroxidase, but they both seem to activate production of HOCl by myeloperoxidase. We conclude here that, first, mercury and methylmercury do not promote direct lipid peroxidation, but that, second, a simultaneous exposure to high inorganic mercury, copper, and iron and low selenium concentrations can lead to a condition in which mercury promotes lipid peroxidations. This mechanism provides a plausible molecular-level explanation for the observed association between high body mercury content and atherosclerosis.
Seppänen
Kari
K
Department of Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Soininen
Pasi
P
Salonen
Jukka T
JT
Lötjönen
Simo
S
Laatikainen
Reino
R
D000818:Animals; D002417:Cattle; D003300:Copper / Q000494:pharmacology*; D004912:Erythrocytes / Q000201:enzymology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008628:Mercury / Q000494:pharmacology*; D009504:Neutrophils / Q000201:enzymology; D019906:Nuclear Magnetic Resonance, Biomolecular; D009195:Peroxidase / Q000378:metabolism
D008077:Lipoproteins, LDL; D003300:Copper; D007501:Iron; D009195:Peroxidase; D005979:Glutathione Peroxidase; D008628:Mercury