SIMULTANEOUS FLUORIDE AND LEAD EXPOSURE ACTING AS A PRO-INFLAMMATORY FACTOR IN DIFFERENTIATED HUMAN THP1 MONOCYTIC CELLS

• Published in: Fluoride Vol. 45; no. 3; pp. 159 - 160
• Main Authors: Baranowska-Bosiacka, I, Dec, K, Gutowska, I, Marchlewicz, M, Kolasa, A, Kondarewicz, A, Wiszniewska, B, Chlubek, D
• Format: Journal Article
• Language: English
• Published: 01-09-2012
• ISSN: 0015-4725

Low-level, chronic exposure of humans to fluorine compounds (F) in the air, water, and food may be atherogenic via the activation of oxidative stress and increased production of reactive oxygen species (ROS). Exposure to lead (Pb) via the same trophic chain may potentiate the intensity of free-radical reactions and changes in lipid metabolism leading to induction and stimulation of the atherosclerosis progression. A long-term exposure can also lead to changes in the amount and catalytic properties of many enzymes, thereby enhancing the inflammatory and proliferation reactions in which a significant role is played by macrophages, which are cells that participate in the formation of atherosclerotic plaques. Early and key changes related to atherogenesis are implicated in oxidation modification of low-density lipoproteins (LDL). Macrophages are of prime importance in this process because of the accumulation of cholesterol originating from LDL and subsequent transformation into foam cells, being the source of locally secreted pro-inflammatory factors. These factors, acting simultaneously with excessive ROS synthesis, are the key ingredients of the development of the inflammatory-proliferative atherogenesis process. Glutathione peroxidase (GPx), by its reducing properties toward a wide range of hydroperoxides, influences the activities of the arachidonic acid metabolism enzymes cyclooxygenases (C0X1 and C0X2). GPx contributes to the detoxification of hydroperoxides and modulation of the synthesis of eicosanoids. The aim of this study was to investigate the influence of simultaneous fluoride and Pb exposure (in concentrations determined in human serum) on the activity of enzymes involved in eicosanoid metabolism: COX1, COX2 (by measuring the products of the enzymes prostaglandin PGE2 and thromboxane TXB2) and GPx1 activity in macrophages obtained from a monocytic line THP-1. THP-1 cells were differentiated into macrophages by administering phorbol myristate acetate (PMA). The THP-1 monocytes were treated with 100 nM PMA for 24 hr, and then the adherent macrophages were incubated for 48 hr with solutions containing NaF and lead acetate (PbAc) at final concentrations of 1, 3, 6, and 10 mu M NaF and 10, 100, 1000 mu M PbAc. These concentrations were selected on the basis of measurements of fluoride and lead levels in human serum from environmental exposure. Simultaneous fluoride and Pb exposure increased the COX-1 and COX-2 activities in macrophages, resulting in the synthesis of the pro-inflammatory factors PGE2 and TXB2 and increased activity of GPx-1 in the macrophages. The observed changes of the enzymes activities occurring in these in vitro cell cultures, with implications for chronic in vivo effects in humans, were probably due to compensation from protection against excessive ROS generated during exposure to fluoride and Pb.