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Mercury (II) alters mitochondrial activity of monocytes at sublethal doses via oxidative stress mechanisms
Author(s) -
Messer Regina L.W.,
Lockwood Petra E.,
Tseng Wan Y.,
Edwards Kerry,
Shaw Melissa,
Caughman Gretchen B.,
Lewis Jill B.,
Wataha John C.
Publication year - 2005
Publication title -
journal of biomedical materials research part b: applied biomaterials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.665
H-Index - 108
eISSN - 1552-4981
pISSN - 1552-4973
DOI - 10.1002/jbm.b.30263
Subject(s) - oxidative stress , chemistry , glutathione , mitochondrion , reactive oxygen species , population , monocyte , oxidative phosphorylation , mitochondrial ros , mercury (programming language) , biochemistry , pharmacology , immunology , biology , medicine , enzyme , computer science , programming language , environmental health
The perennial controversy about the safety of mercury in dental amalgams has adversely affected the availability and the quality of dental care. Chronic Hg(II) blood concentrations above 300 n M are known to alter function of the nervous system and the kidney. However, the effects of blood concentrations of 10 to 75 n M , far more common in the general population, are not clear and mechanisms of any effects are not known. The monocyte is an important potential target of Hg(II) because of its critical role in directing inflammatory and immune responses. In the current study we tested the hypothesis that concentrations of Hg(II) of 10 to 300 n M alter monocyte activity via a redox‐dependent mechanism. Mitochondrial activity was used to establish inhibitory concentrations of Hg(II) following 6 to 72 h of exposures to THP1 human monocytic cells. Then subinhibitory concentrations were applied, and total glutathione levels and reactive oxygen species (ROS) were measured. Antioxidants [ N ‐acetyl cysteine, (NAC); Na 2 SeO 3 , (Se)] and a pro‐oxidant (tert‐butylhydroquinone, tBHQ) were used to support the hypothesis that Hg(II) effects were redox‐mediated. After 72 h of exposure, 20 μ M of Hg(II) inhibited monocytic mitochondrial activity by 50%. NAC mitigated Hg(II)‐induced mitochondrial suppression only at concentrations of greater than 10 μ M , but Se had few effects on Hg‐induced mitochondrial responses. tBHQ significantly enhanced mitochondrial suppression at higher Hg(II) concentrations. Hg(II) concentrations of 75 and 300 n M (0.075 and 0.30 μ M , respectively) significantly increased total glutathione levels, and NAC mitigated these increases. Se plus Hg(II) significantly elevated Hg‐induced total cellular glutathione levels. Increased ROS levels were not detected in monocytes exposed to mercury. Hg(II) acts in monocytic cells, at least in part, through redox‐mediated mechanisms at concentrations below those commonly associated with chronic mercury toxicity, but commonly occurring in the blood of some dental patients. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005