Role of neutrophils in acrylonitrile-induced gastric mucosal damage

Hamdy, Nadia M.; Alghamdi, Hassan A.; Tolba, Mai F.; Esmat, Ahmed; Abdel-Naim, Ashraf B.

doi:10.1016/j.toxlet.2011.10.018

Cited by 9 publications

(3 citation statements)

References 39 publications

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“…Microglia are the resident macrophages of the brain responsible for responding to injury and inflammation. Astrocytes have been shown to secrete inflammatory mediators, such as tumor necrosis factor-α (TNF-α), following ACN exposure, and neutrophil infiltration has been shown to be involved in ACN-induced gastric mucosal damage (Hamdy et al, 2012; Jacob and Ahmed, 2003), suggesting a role for inflammatory cells in ACN-induced toxicity. To our knowledge, this is the first study to investigate the effects of ACN on primary microglia and compare their responses to primary astrocytes treated with ACN.…”

Section: Discussionmentioning

confidence: 99%

Differential response to acrylonitrile toxicity in rat primary astrocytes and microglia

Caito

Aschner

2013

NeuroToxicology

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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.

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Section: Discussionmentioning

confidence: 99%

Differential response to acrylonitrile toxicity in rat primary astrocytes and microglia

Caito

Aschner

2013

NeuroToxicology

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“…For example, damage produced by acrylonitrile in the forestomach was suggested to involve activation of neutrophils and an increase in myeloperoxidase activity, which subsequently stimulated acrylonitrile biotransformation to cyanide. 151 Also, depletion of GSH in combination with release of tissue-damaging radicals from neutrophils can exacerbate tissue damage.…”

Section: Review Of Key Characteristics Of Acrylonitrile Relevant To I...mentioning

confidence: 99%

Acrylonitrile induction of rodent neoplasia: Potential mechanism of action and relevance to humans

Kobets

Iatropoulos

Williams

2022

Toxicology Research and Application

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Acrylonitrile, an industrial chemical, is a multisite carcinogen in rats and mice, producing tumors in four tissues with barrier function, that is, brain, forestomach, Zymbal’s gland, and Harderian gland. To assess mechanism(s) of action (MoA) for induction of neoplasia and to evaluate whether the findings in rodents are indicative of human hazard, data on the potential key effects produced by acrylonitrile in the four rodent target tissues of carcinogenicity were evaluated. A notable finding was depletion of glutathione in various organs, including two target tissues, the brain, and forestomach, suggesting that this effect could be a critical initiating event. An additional combination of oxidative DNA damage and cytotoxic effects of acrylonitrile and its metabolites, cyanide, and 2-cyanoethylene oxide, could initiate pro-inflammatory signaling and sustained cell and tissue injury, leading to compensatory cell proliferation and neoplastic development. The in vivo DNA-binding and genotoxicity of acrylonitrile has been studied in several target tissues with no compelling positive results. Thus, while some mutagenic effects were reported in acrylonitrile-exposed rodents, data to determine whether this mutagenicity stems from direct DNA reactivity of acrylonitrile are insufficient. Accordingly, the induction of tumors in rodents is consistent primarily with a non-genotoxic MoA, although a contribution from weak mutagenicity cannot be ruled out. Mechanistic data to support conclusions regarding human hazard from acrylonitrile exposure is weak. Comparison of metabolism of acrylonitrile between rodents and humans provide little support for human hazard. Three of the tissues affected in bioassays (forestomach, Zymbal’s gland, and Harderian gland) are present only in rodents, while the brain is anatomically different between rodents and humans, diminishing relevance of tumor induction in these tissues to human hazard. Extensive epidemiological data has not revealed causation of human cancer by acrylonitrile.

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“…While the America National Institute for Occupational Safety and Health recommended permissible exposure level to ACN is relatively low (1 ppm), high-level exposure may be reached via skin contact in the case of accidental exposure (8). Studies performed on animals indicated that ACN exhibits mutagenic, embryotoxic (9), carcinogenic, immunotoxic (10) and hematotoxicity (11) effects. An earlier study demonstrated that blood retains high levels of ACN (12) and indicated a metabolic incorporation and macromolecular interaction of ACN in the liver, spleen, bone marrow, lung and adipose tissues of rats (13).…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic effects of acrylonitrile on human umbilical cord mesenchymal stem cells in vitro

Sun

Xie

et al. 2013

Molecular Medicine Reports

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The effects of acrylonitrile (ACN) on human umbilical cord mesenchymal stem cells (hUC‑MSCs) remain unknown. The proliferation, differentiation, clonogenicity and apoptosis effects of ACN and/or N‑acetyl‑L‑cysteine (NAC) on hUC‑MSCs were investigated. The results showed that although ACN at a concentration of 0.1 µg/ml did not affect proliferation or the morphology of hUC‑MSCs compared with the control, osteogenic differentiation and the positive rate of alkaline phosphatase staining in the experimental group were significantly lower compared with the control (P<0.01). All of the effects of ACN were counteracted using NAC, a typical antioxidant. Using a flow cytometry assay, it was observed that ACN induced apoptosis in hUC‑MSCs. The results indicated that the toxic effect produced by ACN on hUC‑MSCs is based on a redox mechanism.

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Role of neutrophils in acrylonitrile-induced gastric mucosal damage

Cited by 9 publications

References 39 publications

Differential response to acrylonitrile toxicity in rat primary astrocytes and microglia

Differential response to acrylonitrile toxicity in rat primary astrocytes and microglia

Acrylonitrile induction of rodent neoplasia: Potential mechanism of action and relevance to humans

Cytotoxic effects of acrylonitrile on human umbilical cord mesenchymal stem cells in vitro

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