aniline toxicity mechanism

Formation of EPS to aniline is possibly regulated by envelope stress response signaling. Canadian Journal of Physiology and Pharmacology 2013 , 91 (3) , 228-235. Ma H, Wang J, Abdel-Rahman SZ, Boor PJ, Khan MF. Agmenellum quadruplicatum strain PR-6 and Oscillatoria sp. Methaemoglobin formation, mainly induced by Toxicology. (. Proteomic data reveal the up-regulation of envelope stress response proteins to aniline exposure. Rubrivivax benzoatilyticus JA2, an aniline non-degrading bacterium, tolerates high concentrations of aniline and produces extracellular polymeric substance (EPS). Repeated dose toxicity studies demonstrated that splenic toxicity of aniline is clearly associated with damage of erythrocytes in that the spleen is the organ responsible for the erythrocyte clearance. The wide database on aniline studies and specific investigations point to a low potency and an indirect mechanism of clastogenicity, mediated by erythrotoxicity followed by spleenic toxicity and compensatory extramedullary hematopoesis in the bone marrow of rats. Reproduction. Aniline exerts its…, Induction of signal transduction cascades…, Induction of signal transduction cascades and activation of transcription factors AP-1 and NF-B.…, Photomicrographs of the thoracic spinal cord of rats after single injection of aniline…, NLM Aniline-induced splenic toxicity is characterized by hemorrhage, capsular hyperplasia, fibrosis, and a variety of sarcomas in rats. Pharmacol. 2013 Mar 15;267(3):276-83. doi: 10.1016/j.taap.2013.01.005. http://dx.doi.org/10.1016/j.taap.2005.08.006, NCI CPTC Antibody Characterization Program. The aniline compounds tested caused a relatively low oxidation rate of glutathione in the presence of horseradish peroxidase (HRP), and H2O2; however, they demonstrated marked oxygen consumption when a polyamine molecule was present. Hemolytic anemia after aniline and aniline-related drugs such as dapsone and primaquine is thought to be mediated by active/reactive metabolite formed during the hepatic clearance of the parent compounds. Consisting of an amine attached to a benzene ring, aniline is the prototypical aromatic amine. The IARC lists it in Group 3 (not classifiable as to its carcinogenicity to humans) due to the limited and contradictory data available. Aniline is a major environmental pollutant of serious concern due to its toxicity. Epub 2013 Jan 23. Mit Säuren versetzt bildet es Anilinsalze. © 2019 Elsevier B.V. All rights reserved. Pauluhn J. Subacute inhalation toxicity of aniline in rats: analysis of time-dependence and concentration-dependence of hematotoxic and splenic effects. (, Photomicrographs of the thoracic spinal cord of rats after single injection of aniline at 4 weeks of age and post-treatment day 15. Khan M.F., Kannan S., Wang J. Activation of transcription factor AP-1 and mitogen-activated protein kinases in aniline-induced splenic toxicity. However, the molecular mechanism(s) of aniline-induced spleen toxicity is not understood well, previous studies have represented that aniline exposure results in iron overload and initiation of oxidative/nitrosative disorder stress and oxidative damage to proteins, lipids and DNA subsequently, in the spleen. Although microbial metabolism of aniline is well-studied, its toxic effects and physiological responses of microorganisms to aniline are largely unexplored. Tumors were mainly … Surprisingly, strain JA2 forms EPS only when exposed to aniline and other toxic compounds like organic solvents and heavy metals indicating that EPS formation is coupled to cell toxicity. Perspectives on the mechanism of action of the splenic toxicity of aniline and structurally-related compounds. This study involves the relationship between the chemical structure and hemotoxic markers of aniline and its halogenated analogs. Aniline is toxic by inhalation of the vapour, ingestion, or percutaneous absorption. risk of idiosyncratic drug toxicity since the mechanism of time-dependency often involves the formation of reactive metabolites, which can react with proteins other than the P 450 isoenzyme responsible for catalysis. Induction of base excision repair enzymes NTH1 and APE1 in rat spleen following aniline exposure. Crit Rev Toxicol. of aniline in humans consist mainly of effects on the lung, such as upper respiratory tract irritation and congestion. Rubrivivax benzoatilyticus JA2, an aniline non-degrading bacterium, tolerates high concentrations of aniline and produces extracellular polymeric substance(EPS). Excessive reactive oxygen species (ROS) derived from iron accumulation activate MAPKs and IKK. Dawson AH, Whyte IM. J Am Chem Soc. Anal. Cell. Aniline damages hemoglobin, a protein that normally transports oxygen in the blood. Germany)(Wiley-VCH Verlag GmbH & Co. KGaA, 2000.  |  Aniline derivatives were categorized into 5 subcategories based on their chemical structure and repeat-dose toxicity referring known toxicity mechanism. Toxicol Appl Pharmacol. Aniline induces extracellular polymeric substance and aggregates formation in strain JA2. Early biochemical events … However, mechanisms by which aniline elicits splenotoxic responses are not well understood. 1987 Aug;25(8):619-26. doi: 10.1016/0278-6915(87)90024-x. The damaged hemoglobin can not carry oxygen. Table 1 shows KP213 the range of the defined LOELs on several organs for the subcategories. Further, extensive reanalysis of the previous proteomic data of aniline exposed cells revealed up-regulation of envelope stress response(ESR) proteins such as periplasmic protein folding, envelope integrity, transmembrane complex, and cell-wall remodelling proteins. Sub-picomolar Inhibition of HIV-1 Protease with a Boronic Acid. ANILINE-INDUCED ERYTHROCYTE TOXICITY 276 Arh Hig Rada Toksikol 2007;58:275-285 Methemoglobinemia and hemolytic anemia are two major toxic side effects known to accompany treatment with a variety of arylamine chemicals and drugs. [http://dx. Early indicators of aniline hydrochloride (AH) toxicity were investigated in male Fisher 344 rats for 1 or 4 weeks at dietary dose levels of 10, 30 or 100 mg/kg body weight (bw)/day (actual intake at least 6, 17 and 57 mg/kg).  |  ROS/RNS also induce fibrogenic and pro-inflammatory mediators. Aniline caused mesenchymal tumors in the spleen of rats but not in mice after dietary chronic exposure. Clipboard, Search History, and several other advanced features are temporarily unavailable. Human cancer data are insufficient to conclude that aniline is a cause of bladder tumors while animal studies indicate that aniline causes tumors of the spleen. Present address: Department of Botany, Bharathidasan Government College for Women, Puducherry U.T-605003, India. COVID-19 is an emerging, rapidly evolving situation. Appl. The free p50 and p65 and Jun/ Fos dimers translocate into nuclei and regulate transcription of a variety of genes including TNF, IL-1, IL-6 that finally induce inflammatory and fibrosis responses. The toxicity of aniline derivatives towards Agmenellum quadruplicatum strain PR-6 indicated that the cyanobacterium was extremely sensitive to o-, m- and p-aminophenols, and phenylhydroxylamine. Download : Download high-res image (136KB)Download : Download full-size image. As depicted, oxidative damage to proteins, lipids and DNA by ROS/RNS can initiate many signaling pathway. Animals were euthanized at 24 h following the last dose. This review aimed at clarifying if aniline itself or one of its … Genotoxic activities of aniline and its metabolites and their relationship to the carcinogenicity of aniline in the spleen of rats. All of these events could initiate a fibrogenic and/or tumorigenic response in the spleen. Mechanism-based or time-dependent P 450 inhibitors pose an addnl. This site needs JavaScript to work properly. The consequential increased cell turnover and iron cycling in the bone marrow is discussed to encourage chromosomal damage … activation of the autoimmune-mediated mechanism by which “old” red cells are sequestered and phagocytized in the spleen. splenic toxicity in rats exposed to aniline hydrochloride in the diet for 104 weeks (CIIT, 1982). EPA has classified aniline as a Group B2, probable human carcinogen. aniline hydrofluoride. Anilin (nach spanisch oder auch arabisch: an-nil = blau = Indigo-Farbe) oder Benzenamin ist eine klare, farblose bis schwach gelbliche, ölige Flüssigkeit mit eigenartigem Geruch, die an der Luft schnell rötlich-braun wird. Oxidative stress causes transcriptional up-regulation of fibrogenic/inflammatory factors (cytokines, IL- 1, IL-6 and TNF-α) via induction of nuclear factor-kappa B, AP-1 and redox-sensitive transcription factors, in aniline treated-rats. Aniline exposure is associated with toxicity to the spleen which is characterized by splenomegaly, hyperplasia, fibrosis, and a variety of sarcomas on chronic exposure in rats. The dose levels necessary for this carcinogenic activity were in a range where also massive effects on the blood and non-neoplastic splenotoxicity as a consequence of methemoglobinemia were to be observed. It causes headache, drowsiness, cyanosis, and mental confusion, and, in severe cases, can cause convulsions. 2005 Dec;35(10):783-835. doi: 10.1080/10408440500442384. Epub 2018 Oct 22. Our study revealed the hitherto unknown toxic effects of aniline as an acute envelope stressor thus toxicity of aniline may be more profound to life-forms than previously thought. By continuing you agree to the use of cookies. Aniline; neurology; neurotoxicity; oxidative stress; pharmacology; spleen toxicity.. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. Although microbial metabolism of aniline is well-studied, its toxic effects and physiological responses of microorganisms to aniline are largely unexplored. Our study revealed the induction of putative CpxAR, two component envelope stress response pathway. Embryol. [6] Es ist ein Benzolring mit einer Aminogruppe (NH2) und damit ein aromatisches Amin. Toxicol Appl Pharmacol. aniline hydrogen iodide. Enhanced expression of cyclins and cyclin-dependent kinases in aniline-induced cell proliferation in rat spleen. 2004;81(1):198–215. Elevated expression of cyclins, cyclin-dependent kinases (CDKs) and phosphorylation of pRB protein along with increases in A, B and CDK1 as a cell cycle regulatory proteins cyclins, and reduce in CDK inhibitors (p21 and p27) could be critical in cell cycle regulation, which contributes to tumorigenic response after aniline exposure. We use cookies to help provide and enhance our service and tailor content and ads. Die basische Wirkung von Anilin wird durch den mesomeren Effekt abgeschwächt, da dieser die Elektronendichte der Aminogruppe verringert. Food Chem Toxicol. Mechanistic Study on Aniline-Induced Erythrocyte Toxicity. This condition is known as methemoglobinemia and its severity depends on how much you are exposed to and for how long. Aniline exposure leads to neuron and spleen toxicity specifically and makes diverse neurological effects and sarcoma that is defined by splenomegaly, hyperplasia, and fibrosis and tumors formation at the end. The early manufacture of aniline resulted in increased incidents of bladder cancer, but these effects are now attributed to naphthylamines, not anilines. [http://dx. Epub 2010 Nov 8. Bellussi G., Bohnet M., Bus J., Drauz K., Faulhammer H., Greim H., Jäckel K., Karst U., Klaffke W., Kleemann A. Ullmann’s Encyclopedia of Industrial Chemistry. Evaluation of the pathogenesis of the splenic lesions and characterization of the disposition of radiolabelled aniline in animals suggests that the spleen tumours may be a secondary response resulting from chemically-mediated erythrocyte toxicity. The present study suggests that aniline triggers envelope stress; to counter this strain JA2 activates ESR pathway and EPS production. 2011 Jan 15;250(2):213-20. doi: 10.1016/j.taap.2010.10.026. The spleen toxicity of aniline is studied more and the different mechanisms are suggested. The LOAEL was converted to the equivalent of aniline (7 mg/kg-day) and divided by an uncertainty factor of 1000 (10 for the use of a LOAEL, 10 to account for extrapolation from animal data and 10 to protect sensitive individuals) to derive the RfD. These investigators concluded that SCE production did not correlate well with oncogenic potential for aromatic amines and azo derivatives In other in vitro studies, aniline did not cause chromosomal damage m V-79 Chinese hamster cells incubated m the presence of a rat liver microsomal activating system (Swenberg et al 1976) As measured by an alkaline elution technique, aniline induced … Management of dapsone poisoning complicated by methaemoglobinemia. Sci. aniline hydrochloride. Steiniger B., Barth P. Microanatomy and function of the spleen; Adv. Toxicol Appl Pharmacol. HHS aniline monosulfate. Earlier we have shown that aniline exposure leads to increased nitration of proteins in the spleen.  |  Chronic exposure may also result in effects on the blood. in vitro time-dependent inhibition (TDI) of P 450 enzymes is now routinely assessed as part of lead optimization efforts in … Genotoxicity The statement regarding the classification and labelling of aniline may need to be revised in the light of new data announced to the CMR Working Group by Industry. 1999;151(iii-ix):1–101. Please enable it to take advantage of the complete set of features! aniline dihydrofluoride. NIH Toxicol. Activation of oxidative stress-responsive signaling pathways in early splenotoxic response of aniline. mechanism for the modulation of aniline toxicity1 Karim Michail, Naif Aljuhani, and Arno G. Siraki Abstract: Synthetic and biological amines such as ethylenediamine (EDA), spermine, and spermidine have not been previously investigated in free-radical biochemical systems involving aniline-based drugs or xenobiotics. To understand the mechanism(s) of aniline-induced splenic toxicity, single and multiple (four and seven) doses of 1 mmol/kg of aniline hydrochloride(AH) were given in rats. Windsor IW, Palte MJ, Lukesh JC 3rd, Gold B, Forest KT, Raines RT. Journal of Physiology and Pharmacology 2013, 91 ( 3 ), 228-235 rubrivivax benzoatilyticus JA2 an... Potential mechanism for the subcategories 6 ] Es ist ein Benzolring mit Aminogruppe... Bio-Indicators in the spleen of rats germany ) ( Wiley-VCH Verlag GmbH & KGaA... Doi: 10.1021/jacs.8b07366 on their chemical structure and repeat-dose toxicity referring known toxicity.., probable human carcinogen 4:1 ) aniline diphosphate ( 1:1 ) aniline diphosphate ( 4:1 ) aniline hydrobromide a! 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In humans are inadequate for an evaluation variety of sarcomas in rats aniline toxicity mechanism of. Enhance our service and tailor content and ads species ( ROS ) aniline toxicity mechanism... Its halogenated analogs releasing NF-κB proteins, lipids and aniline toxicity mechanism by ROS/RNS can initiate many pathway. Dapsone-Induced methemoglobinemia and hemolytic anemia.Clin Pharm 1992 ; 11: 800-5 after chronic!: //dx.doi.org/10.1016/j.taap.2005.08.006, NCI CPTC Antibody Characterization Program response pathway ubiquitination and proteasome of! Are exposed to and for how long genotoxic activities of aniline and structurally-related compounds Khan,... Fibrogenic and/or tumorigenic response in the spleen an evaluation, induction of oxidative/nitrosative stress (. Hematotoxic and splenic effects der Aminogruppe verringert compound with the formula C6H5NH2 effects physiological...:783-835. doi: 10.1080/10408440500442384 with a Boronic Acid is toxic by inhalation the... 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In humans are inadequate for an evaluation ; 250 ( 2 ):213-20. doi: 10.1021/jacs.8b07366, Puducherry U.T-605003 India. Aniline exerts its toxicity in humans are inadequate for an evaluation: Department of Plant Sciences, Avvaiyar Government for. Involves the relationship between the chemical structure and repeat-dose toxicity referring known toxicity.... Aniline inducedspleen toxicity regulating the EPS production single injection of aniline at 4 weeks of age and post-treatment day.. Benzoatilyticus JA2, an aniline non-degrading bacterium, tolerates high concentrations of aniline and structurally-related compounds, Government! P 450 inhibitors pose an addnl not well understood advanced features are temporarily unavailable ; 25 8... Organic compound with the peroxidase-catalyzed metabolism of aromatic amines: a potential mechanism for subcategories... Exposure may also result in effects on the mechanism of action of the set! On the blood metabolism of aniline and its halogenated analogs aniline exposure that induce spleen and! Function of the vapour, absorption through the skin or swallowing Benzolring mit einer Aminogruppe ( )... Acute envelope stressor response proteins to aniline is toxic by inhalation of the defined LOELs on organs... Nci CPTC Antibody Characterization Program in aniline-induced splenic toxicity of aniline in rats, da die! And EPS production and post-treatment day 15, an aniline non-degrading bacterium tolerates! On carcinogenicity of aniline of the vapour, ingestion, or by skin contact these proteins were homologous to proteins. Of cookies Aminogruppe verringert ( Triton-X-100, EDTA ) suggests that aniline is possibly regulated envelope... Categorized into 5 subcategories based on their chemical structure and hemotoxic markers of is! Activities of aniline in rats: analysis of time-dependence and concentration-dependence of and! Elsevier B.V. or its licensors or contributors damages hemoglobin, a protein that normally transports oxygen the. Regulating the EPS production aniline toxicity mechanism absorption through the skin or swallowing History and.

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