title: Differential response to acrylonitrile toxicity in rat primary astrocytes and microglia.
abstract: Acrylonitrile (ACN) is a widely used chemical in the production of plastics, resins, nitriles, acrylic fibers, synthetic rubber and acrylamide. While acute high level exposures to ACN are known to be lethal, chronic low dose exposures causes glial cell tumors in rats. Recently, these glial tumors have been characterized as microglial in origin. While effects of ACN on astrocytes, the more numerous glial cell, have been investigated, the effects on microglia are unknown. This study was conducted to compare the responses of astrocytes and microglia to ACN treatment in vitro to address differential sensitivities and adaptive responses to this toxic chemical. Cell viability, ACN uptake, lipid peroxidation byproducts (F2-isoprostanes), glutathione (GSH) levels and expression of NF-E2-related factor 2 (Nrf2) were evaluated in primary rat microglia and astrocytes following ACN treatment. Results indicate that microglia are more sensitive to ACN than astrocytes, accumulating less ACN while demonstrating higher F2-isoprostane levels. GSH levels were up-regulated in both cell types, as a protective mechanism against ACN-induced oxidative stress, while Nrf2 levels were only induced in microglia. Our data suggest that microglia and astrocytes exhibit different sensitivities and responses to ACN, which are linked to the intracellular thiol status inherent to each of these cell types.
authors.affiliation: Division of Clinical Pharmacology and Pediatric Toxicology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232-0414, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Caito
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Yu
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
mesh_terms: D000097:Acetonitriles / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D028441:F2-Isoprostanes / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000097:Acetonitriles; D028441:F2-Isoprostanes; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D005978:Glutathione; C032159:acetonitrile