The Effects of LXR Agonist TO901317 on Inorganic Mercury Toxicity in Human Astrocytes

Abstract

Inorganic mercury is toxic to human neuronal and glial cells. Oxidative stress due to increased reactive oxygen species (ROS) is one of the major causes of inorganic mercury toxicity leading to cell death. In vivo and in vitro studies indicated that the liver X receptor (LXR) agonists could be beneficial for stroke and neurodegenerative diseases. However, their effects on astrocyte functions remain unclear. This study aims to investigate the effects of LXR agonist TO901317 on human astrocyte viability and its effect on inorganic mercury (mercuric chloride, HgCl₂)-induced cell death. Cell viability of human astrocytoma U373 cells was measured by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The elevation of ROS and lipid peroxidation were detected by measuring fluorescence intensity of dichlorofluorescein (DCF) and levels of malondialdehyde (MDA), respectively. Herein, TO901317 at 50 µM reduced more than 75% cell viability at 24 hours post-exposure while lower concentrations, 0.1-10 µM, were not toxic to U373 cells. Pretreatment with these non-toxic concentrations of TO901317 for 24 hours could not prevent the loss of cell viability induced by 30 µM HgCl₂ at 24 hours post-exposure. TO901317 at 10 µM could decrease MDA levels by 44%. However, pretreatment with TO901317 did not alter the levels of DCF fluorescence intensity and MDA caused by 10 and 30 µM HgCl₂ after exposure for 1 and 24 hours. These results suggested that an LXR agonist TO901317 could not protect toxicity of inorganic mercury on human astrocytes and has no effect on the increased ROS and lipid peroxidation induced by inorganic mercury.