title: Exposure of rat hippocampal astrocytes to Ziram increases oxidative stress.
abstract: Pesticides have been shown in several studies to be the leading candidates of environmental toxins and may contribute to the pathogenesis of several neurodegenerative diseases. Ziram (zinc-bis(dimethyldithiocarbamate)) is an agricultural dithiocarbamate fungicide that is used to treat a variety of plant diseases. In spite of their generally acknowledged low toxicity, dithiocarbamates are known to cause a wide range of neurobehavioral effects as well as neuropathological changes in the brain. Astrocytes play a key role in normal brain physiology and in the pathology of the nervous system. This investigation studied the effects of 1.0 µM Ziram on rat hippocampal astrocytes. The thiobarbituric acid reactive substance assay performed showed a significant increase in malondialdehyde, a product of lipid peroxidation, in the Ziram-treated cells. Biochemical analysis also revealed a significant increase in the induction of 70 kDa heat shock and heme oxygenase 1 stress proteins. In addition, an increase of glutathione peroxidase (GPx) and a significant increase in oxidized glutathione (GSSG) were observed in the Ziram-treated cells. The ratio GSH to GSSG calculated from the treated cells was also decreased. Light and transmission electron microscopy supported the biochemical findings in Ziram-treated astrocytes. This data suggest that the cytotoxic effects observed with Ziram treatments may be related to the increase of oxidative stress.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St John's University, New York City, USA.
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Matei
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St John's University, New York City, USA trombetl@stjohns.edu.
authors.forename: Louis D
authors.initials: LD
authors.lastname: Trombetta
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D002478:Cells, Cultured; D005659:Fungicides, Industrial / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015039:Ziram / Q000633:toxicity*
chemical_list: D005659:Fungicides, Industrial; D015039:Ziram
keywords: Ziram; astrocytes; oxidative stress; pesticide; stress proteins