Possible Functional Immunotoxicity of Acrylonitrile (Vcn)

Hamada, Farid M.A.; Abdel-Aziz, A.H.; Abd-Allah, Adel R. A.; Ahmed, Aqsa

doi:10.1006/phrs.1997.0264

Cited by 18 publications

(5 citation statements)

References 4 publications

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“…ACN is possibly carcinogenic to humans [Group 2B] [2]. Animal studies indicated that ACN possesses mutagenic [12], carcinogenic [13], immunotoxic [14], embryotoxic [15] and neurotoxic properties [16]. Clinical studies indicated increased risk of lung cancer, brain cancer and renal cell carcinoma in some exposure categories 17,18].…”

Section: Bacgroundmentioning

confidence: 99%

Acrylonitrile-induced Gastric Toxicity in Rats: Role of Xanthine Oxidase

Al-Abbasi

2012

Med Sci Monit

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SummaryBackgroundAcrylonitrile (ACN) is an extensively produced aliphatic nitrile. The gastrointestinal tract is an important target organ for ACN toxicity. The objective of the present study was to investigate the role of xanthine oxidase (XO) in ACN-induced gastric toxicity in rats.Material/MethodsWe assessed the effect of ACN on oxidative stress parameters as xanthine oxidase (XO) and total xanthine dehydrogenase (XD)/ XO activity, superoxide anion (O2·−) production, reduced glutathione (GSH) levels and lipid peroxidation in gastric tissues.ResultsA single oral dose of ACN (25 mg/kg) caused a significant enhancement in XO activity. ACN also caused a significant depletion of GSH levels, enhanced O2·− production and increased lipid peroxidation in the time-course experiment. In the dose-response experiment, ACN accelerated the conversion of XD to XO, with a significant depletion of gastric GSH in a dose-related manner. A strong negative correlation existed between the levels of GSH and the percentage enhancement in XO activity (r =−0.997). (O2·−) production and malondialdehyde (MDA) formation were significantly elevated in a dose-related manner. Pretreatment with allopurinol (50 mg/kg) significantly protected against ACN-induced rise in XO activity, depletion of GSH, and elevated production of (O2·−). However, pretreatment with diethyl maleate (DEM; 100 mg/kg) significantly aggravated the ACN-induced GSH depletion and rise in XO activity. Furthermore, DEM significantly enhanced (O2·−) and MDA production.ConclusionsThe present study indicates that enhancement of XO activity could be implicated in ACN-induced gastric damage in rats.

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Section: Bacgroundmentioning

confidence: 99%

Acrylonitrile-induced Gastric Toxicity in Rats: Role of Xanthine Oxidase

Al-Abbasi

2012

Med Sci Monit

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“…Additionally, ACN has been found to contaminate the environment, possibly from burning of plastics and industrial waste discharge (IARC, 1999). ACN is a potent toxic chemical which can cause acute irritation of soft tissues, gastric bleeding, immunotoxicity and neurotoxicity in animals (Gagnaire et al, 1998;Hamada et al, 1998;IARC, 1999). Chronic administration of ACN resulted in tumors in multiple organs of rodents including brain, lung, stomach and mammary gland.…”

Section: Introductionmentioning

confidence: 99%

Acrylonitrile induced apoptosis via oxidative stress in neuroblastoma SH‐SY5Y cell

Watcharasit

Suntararuks

Visitnonthachai

et al. 2010

J of Applied Toxicology

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Acrylonitrile (ACN) is a chemical that is widely used in the production of plastics, acrylic fibers, synthetic rubbers and resins. It has been reported that ACN can cause oxidative stress, a condition which is well recognized as an apoptotic initiator; however, information regarding ACN-induced apoptosis is limited. This present study investigated whether ACN induces apoptosis in human neuroblastoma SH-SY5Y cells, and whether its apoptotic induction involves oxidative stress. The results showed that ACN caused activation of caspase-3, a key enzyme involved in apoptosis, in a dose- and time-dependent manner. Detection of sub-G1 apoptotic cell death and apoptotic nuclear condensation revealed that ACN caused an increase in the number of apoptotic cells indicating ACN induces apoptosis in SH-SY5Y cells. ACN dose- and time-dependently increased the level of proapoptotic protein, Bax. Pretreatment with N-acetylcysteine (NAC), an antioxidant, attenuated caspase-3 activation by ACN, as evidenced by a reduction in proteolysis of PARP, a known caspase-3 substrate, as well as in the number of sub-G1 apoptotic cells. Moreover, induction of Bax by ACN was abolished by NAC. Taken together, the results indicate that ACN induces apoptosis in SH-SY5Y cells via a mechanism involving generation of oxidative stress-mediated Bax induction.

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“…153 According to the authors this might create a favorable condition for carcinogenicity. In an earlier study by Hamada et al 154 acrylonitrile also produced an immunosuppressive effect in CD-1 mice, decreasing the number of IgA producing cells in the intestines and a significant depletion of spleen lymphocyte population, which could be a contributing factor to the carcinogenicity of acrylonitrile in the forestomach.…”

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

confidence: 86%

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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Possible Functional Immunotoxicity of Acrylonitrile (Vcn)

Cited by 18 publications

References 4 publications

Acrylonitrile-induced Gastric Toxicity in Rats: Role of Xanthine Oxidase

Acrylonitrile-induced Gastric Toxicity in Rats: Role of Xanthine Oxidase

Acrylonitrile induced apoptosis via oxidative stress in neuroblastoma SH‐SY5Y cell

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

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