Inorganic arsenic causes cell apoptosis in mouse cerebrum through an oxidative stress-regulated signaling pathway
Journal
Archives of Toxicology
Journal Volume
85
Journal Issue
6
Pages
565-575
Date Issued
2011
Author(s)
Abstract
Arsenic pollution is a major public health problem worldwide. Inorganic arsenic (iAs) is usually more harmful than organic ones. iAs pollution increases the risk of human diseases such as peripheral vascular disease and cancer. However, the toxicological effects of iAs in the brain are mostly unclear. Here, we investigated the toxic effects and possible mechanisms of iAs in the cerebrum of mice after exposure to iAs (0.5 and 5 ppm (mg/l) As 2O3, via the drinking water), which was the possible human exposed dose via the ingestion in iAs-contaminated areas, for 6 consecutive weeks. iAs dose-dependently caused an increase of LPO production in the plasma and cerebral cortex. iAs also decreased the reduced glutathione levels and the expressions of NQO1 and GPx mRNA in the cerebral cortex. These impairments in the cerebral cortex caused by iAs exposure were significantly correlated with the accumulation of As. Moreover, iAs induced the production of apoptotic cells and activation of caspase-3, up-regulation of Bax and Bak, and down-regulation of Mcl-1 in the cerebral cortex. Exposure to iAs also triggered the expression of ER stress-related genes, including GRP78, GRP94, and CHOP. Meanwhile, an increase of p38 activation and dephosphorylation of ERK1/2 were shown in the cerebral cortex as a result of iAs-exposed mice. These iAs-induced damages and apoptosis-related signals could be significantly reversed by NAC. Taken together, these results suggest that iAs-induced oxidative stress causes cellular apoptosis in the cerebrum, signaling of p38 and ERK1/2, and ER stress may be involved in iAs-induced cerebral toxicity. ? 2011 Springer-Verlag.
Subjects
Apoptosis; ER stress; ERK1/2; Inorganic arsenic; Oxidative stress; p38
SDGs
Other Subjects
acetylcysteine; arsenic; caspase 3; glutathione; mitogen activated protein kinase 1; mitogen activated protein kinase 3; mitogen activated protein kinase p38; reactive oxygen metabolite; animal experiment; animal tissue; apoptosis; article; Bak gene; Bax gene; brain cortex; C EBP homologous protein gene; concentration response; controlled study; endoplasmic reticulum stress; gene; gene expression; glucose related protein 78 gene; glucose related protein 94 gene; glutathione peroxidase gene; lipid peroxidation; male; MCL 1 gene; mouse; NAD(P)H quinone oxidoreductase 1 gene; neurotoxicity; nonhuman; oxidative stress; plasma; priority journal; protein dephosphorylation; upregulation; Acetylcysteine; Animals; Apoptosis; Apoptosis Regulatory Proteins; Arsenic Poisoning; Arsenicals; Cerebral Cortex; Dose-Response Relationship, Drug; Environmental Pollutants; Gene Expression Regulation, Enzymologic; Glutathione; Glutathione Peroxidase; Lipid Peroxides; Male; MAP Kinase Signaling System; Mice; Mice, Inbred ICR; NAD(P)H Dehydrogenase (Quinone); Nerve Tissue Proteins; Neurons; Neuroprotective Agents; Oxidation-Reduction; Oxidative Stress; Oxides; Random Allocation; RNA, Messenger; Mus
Type
journal article