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.

Glutathione-Dependent Detoxification Processes in Astrocytes

“…3d). This enzyme is expressed and active in Acrylonitrile [157] Ammonium [90,158] Anethole dithiolethione [159] Arsenite [91] Arsenate [89] Cadmium chloride [89,91] Catalpol [160] Copper chloride [89,92] Copper oxide nanoparticles [93] Curcumin Thyroid hormone [169] This [78][79][80]. In addition to Mrp1, astrocytes express a number of other Mrps and other potential GSH exporters in culture and in vivo [43, [81][82][83][84][85][86], but the contribution of these transporters in astrocytic export processes remains to be elucidated.…”

Analysis of DNA Adducts and Mutagenic Potency and Specificity in Rats Exposed to Acrylonitrile

“…34−36 While astrocytes and neurons are the major cell types of the central nervous system, microglia are a counterpart to macrophages and act as the major inflammatory cell of the brain and spinal cord by removing damaged neurons and pathogens. 26,37 Microglial cells have an important role in extracellular signaling and also respond to neuronal injury by releasing neurotoxic and neurotrophic factors. All these processes can be modulated by oxidative stress, compromising microglial function and homeostasis.…”

Hydrolytic denitrification and decynidation of acrylonitrile in wastewater with Arthrobacter nitroguajacolicus ZJUTB06-99

“…Furthermore, these emerging pollution sources are highly toxic, carcinogenic (Ramakrishna et al 1989; Thier et al 2000; Quast 2002) and related toxicity investigation has been widely reported, e.g. acrylonitrile could leads to neurobehavioral disorder in rats and some human sicknesses (Caito et al 2013; Khan et al 2009; Tanii and Hashimoto 1984). So it is urgent to explore safe and efficient treatment technology on acrylonitrile wastewater treatment.…”