Browse > Article
http://dx.doi.org/10.1007/s43188-021-00115-z

Neurotoxicity of anthracene and benz[a]anthracene involves oxidative stress-induced neuronal damage, cholinergic dysfunction and disruption of monoaminergic and purinergic enzymes  

Olasehinde, Tosin A. (Nutrition and Toxicology Division, Food Technology Department, Federal Institute of Industrial Research Oshodi)
Olaniran, Ademola O. (Discipline of Microbiology, School of Life Sciences, University of Kwazulu-Natal)
Publication Information
Toxicological Research / v.38, no.3, 2022 , pp. 365-377 More about this Journal
Abstract
In this study, the modulatory effects of anthracene (ANT) and benz[a]anthracene (BEN) on biochemical markers associated with neurodegeneration were assessed in mouse hippocampal neuronal cells (HT-22). Neuronal cells were cultured and exposed to ANT and BEN (25-125 µM) for 5 days, and the cell viability was determined via MTT assay. Morphological characteristics of the cells were assessed using a compound microscope. Biochemical parameters such as acetylcholinesterase (AChE), monoamine oxidase (MAO) and adenosine deaminase (ADA) activities as well as oxidative stress biomarkers (catalase [CAT], glutathione -S- transferase [GST] activities and Glutathione [GSH] levels) and nitric oxide [NO] levels were assessed after cells were treated with ANT and BEN for two days. The results showed that cell viability reduced with an increase in exposure time. After the fifth day of treatment, BEN and ANT (125 µM) reduced percentage viability to 41 and 38.1%, respectively. Light micrographs showed shrinkage of cells, neuronal injury and cell death in cells treated with higher concentrations of BEN and ANT (50 and 125 µM). Furthermore, AChE and MAO activities reduced significantly after treatment for 48 h with ANT and BEN. A significant decrease in CAT and GST activities and low GSH levels were observed after treatment with BEN and ANT. However, both polycyclic aromatic hydrocarbons caused a significant increase in ADA activity and NO levels. These results suggest that ANT and BEN may induce neurodegeneration in neuronal cells via oxidative stress-induced-neuronal injury, disruption of cholinergic, monoaminergic and purinergic transmission, and increased nitric oxide levels.
Keywords
Anthracene; Benz[a]anthrancene; Polycyclic aromatic hydrocarbons; Neurodegeneration; Oxidative stress; Cholinergic deficit; Antioxidant enzymes;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Olasehinde TA, Olaniran AO, Okoh AI (2019) Neuroprotective effects of some seaweeds against Zn - induced neuronal damage in HT-22 cells via modulation of redox imbalance, inhibition of apoptosis and acetylcholinesterase activity. Metab Brain Dis 34:1615-1627. https://doi.org/10.1007/s11011-019-00469-2   DOI
2 Ramesh A, Harris KJ, Archibong AE (2017) Reproductive and developmental toxicology. Chapter 40-reproductive toxicity of polycyclic aromatic hydrocarbons, 2nd edn. Acadmic Press, Elsevier. Edited Ramesh C Gupta. https://doi.org/10.1016/B978-0-12-804239-7.00040-8
3 Jeng HA, Pan C-H, Lin W-Y, Wu M-T, Taylor S, Chang-Chien G-P, Zhou G, Diawara N (2013) Biomonitoring of polycyclic aromatic hydrocarbons from coke oven emissions and reproductive toxicity in nonsmoking workers. J Hazard Mater 244-245:436-443. https://doi.org/10.1016/j.jhazmat.2012.11.008   DOI
4 Hart LJ, Smith SA, Smith BJ, Robertson J, Besteman EG, Holladay SD (1998) Subacute immunotoxic effects of the polycyclic aromatic hydrocarbon 7,12-dimethylbenzanthracene (DMBA) on spleen and pronephros leukocytic cell counts and phagocytic cell activity in tilapia (Oreochromis niloticus). Aquat Toxicol 41:17-29. https://doi.org/10.1016/s0166-445x(97)00075-1   DOI
5 Bollinger CE, McCallister M, Clark R, Rhoades R, Maguire M, Savage RE, Jiao Y, Harris KJ, Ramesh A, Lochotzki H, Hood DB (2020) Polycyclic aromatic hydrocarbons: implications for developmental, molecular, and behavioral neurotoxicity. In: Handbook of toxicology of chemical warfare agents, pp 279-297. Academic Press, Elsevier. Edited by Ramesh C. Gupta. https://doi.org/10.1016/b978-0-12-819090-6.00019-2
6 Saunders CR, Das SK, Ramesh A, Shockley DC, Mukherjee S (2006) Benzo(a)pyrene-induced acute neurotoxicity in the F-344 rat: role of oxidative stress. J Appl Toxicol 26:427-438. https://doi.org/10.1002/jat.1157   DOI
7 Shimada T, Fujii-Kuriyama Y (2004) Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochromes P450 1A1 and1B1. Cancer Sci 95:1-6. https://doi.org/10.1111/j.1349-7006.2004.tb03162.x   DOI
8 Sauer AV, Hernandez RJ, Fumagalli F, Bianchi V, Poliani PL, Dallatomasina C, Riboni E, Politi LS, Tabucchi A, Carlucci F, Casiraghi M, Carriglio N, Cominelli M, Forcellini CA, Barzaghi F, Ferrua F, Minicucci F, Medaglini S, Leocani L, La Marca G, Notarangelo LD, Azzari C, Comi G, Baldoli C, Canale S, Sessa M, D'Adamo P, Aiuti A (2017) Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-defcient mice and patients. Sci Rep 7:40136. https://doi.org/10.1038/srep40136   DOI
9 Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88-95. https://doi.org/10.1016/0006-2952(61)90145-9   DOI
10 Carr AC, McCall MR, Frei B (2000) Oxidation of LDL by myeloperoxidase and reactive nitrogen species: reaction pathways and antioxidant protection. Arterioscler Thromb Vasc Biol 20:1716-1723. https://doi.org/10.1161/01.atv.20.7.1716   DOI
11 Rengarajan T, Rajendran P, Nandakumar N, Lokeshkumar B, Rajendran P, Nishigaki I (2015) Exposure to polycyclic aromatic hydrocarbons with special focus on cancer. Asian Pac J Trop Biomed 5:182-189. https://doi.org/10.1016/s2221-1691(15)30003-4   DOI
12 Wang J, Li C-L, Tu B-J, Yang K, Mo T-T, Zhang R-Y, Cheng S-Q, Chen C-Z, Jiang X-J, Han T-L, Peng B, Baker PN, Xia Y-Y (2018) Integrated epigenetics, transcriptomics, and metabolomics to analyze the mechanisms of Benzo[a]pyrene neurotoxicity in the hippocampus. Toxicol Sci 166:65-81. https://doi.org/10.1093/toxsci/kfy192   DOI
13 Honda M, Suzuki N (2020) Toxicities of polycyclic aromatic hydrocarbons for aquatic animals. Int J Environ Res Public Health 17:1636. https://doi.org/10.3390/ijerph17041363   DOI
14 Badreddine S, Abdelhafdh K, Dellali M, Mahmoudi E, Sheehan D, Hamouda B (2017) The effects of anthracene on biochemical responses of Mediterranean mussels Mytilus galloprovincialis. Chem Ecol 33:309-324. https://doi.org/10.1080/02757540.2017.1309393   DOI
15 Simic G, Babic Leko M, Wray S, Harrington CR, Delalle I, Jovanov-Milosevic N, Bazadona D, Buee L, De Silva R, Di Giovanni G, Wischik CM, Hof PR (2017) Monoaminergic neuropathology in Alzheimer's disease. Prog Neurobiol 151:101-138. https://doi.org/10.1016/j.pneurobio.2016.04.001   DOI
16 Peifer J, Cosnier F, Grova N, Nunge H, Salquebre G, Decret MJ, Cossec B, Rychen G, Appenzeller BM, Schroeder H (2013) Neurobehavioral toxicity of a repeated exposure (14 days) to the airborne polycyclic aromatic hydrocarbon fluorene in adult Wistar male rats. PLoS ONE 8:e71413. https://doi.org/10.1371/journal.pone.0071413   DOI
17 Bai H, Wu M, Zhang H, Tang G (2017) Chronic polycyclic aromatic hydrocarbon exposure causes DNA damage and genomic instability in lung epithelial cells. Oncotarget 8:79034-79045. https://doi.org/10.18632/oncotarget.20891   DOI
18 Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell B 39:44-84. https://doi.org/10.1016/j.biocel.2006.07.001   DOI
19 Ozturk IC, Batcioglu K (2002) Investigation of the relationship between nitric oxide metabolites' levels and adenosine deaminase activity in 7,12-dimethylbenz[a]anthracene induced mouse liver. J Biochem Mol Toxicol 16:260-262. https://doi.org/10.1002/jbt.10041   DOI
20 Marisco PC, Carvalho FB, Rosa MM, Girardi BA, Gutierres JM, Jaques JAS, Salla APS, Pimentel VC, Schetinger MRC, Leal DBR, Mello CF, Rubin MA (2013) Piracetam prevents scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities. Neurochem Res 38:1704-1714. https://doi.org/10.1007/s11064-013-1072-6   DOI
21 Sarma SN, Blais JM, Chan HM (2017) Neurotoxicity of alkylated polycyclic aromatic compounds in human neuroblastoma cells. J Toxicol Environ Health A 80:285-300. https://doi.org/10.1080/15287394.2017.1314840   DOI
22 Sinha A (1972) Colorimetric assay of catalase. Anal Biochem 47:389-394. https://doi.org/10.1016/0003-2697(72)90132-7   DOI
23 Katz IS, Albuquerque LL, Suppa AP, da Silva GB, Jensen JR, Borrego A, Massa S, Starobinas N, Cabrera WH, De Franco M, Borelli P, Ibanez OM, Ribeiro OG (2016) 7,12-Dimethylbenz(a) anthracene-induced genotoxicity on bone marrow cells from mice phenotypically selected for low acute inflammatory response. DNA Repair 37:43-52. https://doi.org/10.1016/j.dnarep.2015.11.006   DOI
24 Patri M, Singh A (2019) Protective effects of noradrenaline on benzo[a]pyrene-induced oxidative stress responses in brain tumor cell lines. In Vitro Cell Dev Biol Anim 55:665-675. https://doi.org/10.1007/s11626-019-00378-9   DOI
25 Olasehinde TA, Olaniran AO, Okoh AI (2020) Sulfated polysaccharides of some seaweeds exhibit neuroprotection via mitigation of oxidative stress, cholinergic dysfunction and inhibition of Zn-induced neuronal damage in HT-22 cells. BMC Complement Med Ther 20:251. https://doi.org/10.1186/s12906-020-03047-7   DOI
26 Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM (2016) Alzheimer's disease: targeting the cholinergic system. Curr Neuropharmacol 14:101-115. https://doi.org/10.2174/1570159X13666150716165726   DOI
27 Stanciu GD, Luca A, Rusu RN, Bild V, Beschea Chiriac SI, Solcan C, Bild W, Ababei DC (2019) Alzheimer's disease pharmacotherapy in relation to cholinergic system involvement. Biomolecules 10:40. https://doi.org/10.3390/biom10010040   DOI
28 Incardona JP, Day HL, Collier TK, Scholz NL (2006) Developmental toxicity of 4-ring polycyclic aromatic hydrocarbons in zebrafish is differentially dependent on AH receptor isoforms and hepatic cytochrome P4501A metabolism. Toxicol Appl Pharmacol 217:308-321. https://doi.org/10.1016/j.taap.2006.09.018   DOI
29 Smith J, Neupane R, McAmis W, Singh U, Chatterjee S, Raychoudhury S (2019) Toxicity of polycyclic aromatic hydrocarbons involves NOX2 activation. Toxicol Rep 6:1176-1181. https://doi.org/10.1016/j.toxrep.2019.11.006   DOI
30 Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70-77. https://doi.org/10.1016/0003-9861(59)90090-6   DOI
31 Vieira LR, Sousa A, Frasco MF, Lima I, Morgado F, Guilhermino L (2008) Acute effects of Benzo[a]pyrene, anthracene and a fuel oil on biomarkers of the common goby Pomatoschistus microps (Teleostei, Gobiidae). Sci Total Environ 395:87-100. https://doi.org/10.1016/j.scitotenv.2008.01.052   DOI
32 Palanikumar L, Kumaraguru AK, Ramakritinan CM, Anand M (2012) Biochemical response of anthracene and benzo [a] pyrene in milkfish Chanos chanos. Ecotoxicol Environ Saf 75:187-197. https://doi.org/10.1016/j.ecoenv.2011.08.028   DOI
33 Miyata M, Furukawa M, Takahashi K, Gonzalez FJ, Yamazoe Y (2001) Mechanism of 7,12-Dimethylbenz[a]anthracene-induced immunotoxicity: role of metabolic activation at the target organ. Jpn J Pharmacol 86:302-309. https://doi.org/10.1254/jjp.86.302   DOI
34 Sperlagh B, Sylvester Vizi E (2011) The role of extracellular adenosine in chemical neurotransmission in the hippocampus and basal ganglia: pharmacological and clinical aspects. Curr Top Med Chem 11:1034-1046. https://doi.org/10.2174/156802611795347564   DOI
35 Cunha RA (2016) How does adenosine control neuronal dysfunction and neurodegeneration? J Neurochem 139:1019-1055. https://doi.org/10.1111/jnc.13724   DOI
36 Kleiner HE, Vulimiri SV, Reed MJ, Uberecken A, Digiovanni J (2002) Role of cytochrome P450 1a1 and 1b1 in the metabolic activation of 7,12-Dimethylbenz[a]anthracene and the effects of naturally occurring furanocoumarins on skin tumor initiation. Chem Res Toxicol 15:226-235. https://doi.org/10.1021/tx010151v   DOI
37 Song M-K, Kim Y-J, Song M, Choi H-S, Park Y-K, Ryu J-C (2012) Formation of a 3,4-diol-1,2-epoxide metabolite of benz[a] anthracene with cytotoxicity and genotoxicity in a human in vitro hepatocyte culture system. Environ Toxicol Pharmacol 33:212-225. https://doi.org/10.1016/j.etap.2011.12.020   DOI
38 Lin Y-C, Wu C-Y, Hu C-H, Pai T-W, Chen Y-R, Wang W-D (2020) Integrated hypoxia signaling and oxidative stress in developmental neurotoxicity of Benzo[a]Pyrene in Zebrafsh Embryos. Antioxidants 9:731. https://doi.org/10.3390/antiox9080731   DOI
39 Yang K, Jiang X, Cheng S, Bai L, Xia Y, Chen C, Meng P, Wang J, Li C, Tang Q, Cao X, Tu B (2019) Synaptic dopamine release is positively regulated by SNAP-25 that involves in benzo[a]pyrene-induced neurotoxicity. Chemosphere 237:124378. https://doi.org/10.1016/j.chemosphere.2019.124378   DOI
40 Slotkin TA, Skavicus S, Ko A, Levin ED, Seidler FJ (2019) The Developmental neurotoxicity of tobacco smoke can be mimicked by a combination of nicotine and Benzo[a]Pyrene: efects on cholinergic and serotonergic systems. Toxicol Sci 167:293-304. https://doi.org/10.1093/toxsci/kfy241   DOI
41 Dulla CG, Dobelis P, Pearson T, Frenguelli BG, Staley KJ, Masino SA (2005) Adenosine and ATP link PCO2 to cortical excitability via pH. Neuron 48:1011-1023. https://doi.org/10.1016/j.neuron.2005.11.009   DOI
42 Holth TF, Tollefsen KE (2012) Acetylcholine esterase inhibitors in effluents from oil production platforms in the North Sea. Aquat Toxicol 112-113:92-98. https://doi.org/10.1016/j.aquatox.2011.10.019   DOI
43 Adefegha SA, Oboh G, Olasehinde TA (2016) Alkaloid extracts from shea butter and breadfruit as potential inhibitors of monoamine oxidase, cholinesterases, and lipid peroxidation in rats' brain homogenates: a comparative study. Comp Clin Pathol 25:1213-1219. https://doi.org/10.1007/s00580-016-2331-0   DOI
44 Di Giovanni G, Svob Strac D, Sole M, Unzeta M, Tipton KF, Muck-Seler D, Bolea I, Della Corte L, Nikolac Perkovic M, Pivac N, Smolders IJ, Stasiak A, Fogel WA, De Deurwaerdere P (2016) Monoaminergic and histaminergic strategies and treatments in brain diseases. Front Neurosci 10:541. https://doi.org/10.3389/fnins.2016.00541   DOI
45 Chen X, Chen Y, Huang C, Dong Q, Roper C, Tanguay RL, Zhu Y, Zhang Y (2019) Neurodevelopmental toxicity assessments of alkyl phenanthrene and Dechlorane Plus co-exposure in zebrafish. Ecotoxicol Environ Saf 180:762-769. https://doi.org/10.1016/j.ecoenv.2019.05.066   DOI
46 Lawal AT (2017) Polycyclic aromatic hydrocarbons. A review. Cogent Environ Sci 3:1339841. https://doi.org/10.1080/23311843.2017.1339841   DOI
47 Naoi M, Riederer P, Maruyama W (2016) Modulation of monoamine oxidase (MAO) expression in neuropsychiatric disorders: genetic and environmental factors involved in type A MAO expression. J Neural Transm 123:91-106. https://doi.org/10.1007/s00702-014-1362-4   DOI
48 Bortolato M, Chen K, Shih JC (2008) Monoamine oxidase inactivation: from pathophysiology to therapeutics☆. Adv Drug Deliv Rev 60:1527-1533. https://doi.org/10.1016/j.addr.2008.06.002   DOI
49 Polachini CRN, Spanevello RM, Casali EA, Zanini D, Pereira LB, Martins CC, Baldissareli J, Cardoso AM, Duarte MF, Da Costa P, Prado ALC, Schetinger MRC, Morsch VM (2014) Alterations in the cholinesterase and adenosine deaminase activities and inflammation biomarker levels in patients with multiple sclerosis. Neuroscience 266:266-274. https://doi.org/10.1016/j.neuroscience.2014.01.048   DOI
50 Nam TH, Jeon HJ, Mo HH, Cho K, Ok YS, Lee SE (2015) Determination of biomarkers for polycyclic aromatic hydrocarbons (PAHs) toxicity to earthworm (Eisenia fetida). Environ Geochem Health 37:943-951. https://doi.org/10.1007/s10653-015-9706-z   DOI
51 Wang F, Yang L, Zhang B, Liu G, Wang C, Zhang Y, Wang T (2020) Neurobehavioral performance of PAH exposure in male coal miners in Shanxi, China: a cross-sectional study. Int Arch Occup Environ Health 93:707-714. https://doi.org/10.1007/s00420-020-01521w   DOI
52 Mastral AM, Callen MS (2000) A review on polycyclic aromatic hydrocarbon (PAH) emissions from energy generation. Environ Sci Technol 34:3051-3057. https://doi.org/10.1021/es001028d   DOI
53 Abdel-Shafy HI, Mansour MSM (2016) A review on polycyclic aromatic hydrocarbons: source, environmental impact, effect on human health and remediation. Egypt J Pet 25:107-123. https://doi.org/10.1016/j.ejpe.2015.03.011   DOI
54 Das SK, Aparna S, Patri M (2020) Chronic waterborne exposure to benzo[a]pyrene induces locomotor dysfunction and development of neurodegenerative phenotypes in zebrafish. Neurosci Lett 716:134646. https://doi.org/10.1016/j.neulet.2019.134646   DOI
55 Chen C, Tang Y, Jiang X, Qi Y, Cheng S, Qiu C, Peng B, Tu B (2012) Early postnatal Benzo(a)pyrene exposure in Sprague-Dawley rats causes persistent neurobehavioral impairments that emerge postnatally and continue into adolescence and adulthood. Toxicol Sci 125:248-261. https://doi.org/10.1093/toxsci/kfr265   DOI
56 Pohanka M (2011) Cholinesterases, a target of pharmacology and toxicology. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 155:219-229. https://doi.org/10.5507/bp.2011.036   DOI
57 Cheng S-Q, Xia Y-Y, He J-L, Liu X-Q, Chen X-M, Ding Y-B, Wang Y-X, Peng B, Tu B-J (2013) Neurotoxic effect of subacute benzo(a)pyrene exposure on gene and protein expression in Sprague-Dawley rats. Environ Toxicol Pharmacol 36:648-658. https://doi.org/10.1016/j.etap.2013.06.008   DOI
58 Gauthier PT, Norwood WP, Prepas EE, Pyle GG (2016) Behavioural alterations from exposure to Cu, phenanthrene, and Cuphenanthrene mixtures: linking behaviour to acute toxic mechanisms in the aquatic amphipod, Hyalella azteca. Aquat Toxicol 170:377-383. https://doi.org/10.1016/j.aquatox.2015.10.019   DOI
59 Tang Y, Donnelly KC, Tiffany-Castiglioni E, Mumtaz MM (2003) Neurotoxicity of polycyclic aromatic hydrocarbons and simple chemical mixtures. J Toxicol Environ Health A 66:919-940. https://doi.org/10.1080/15287390306455   DOI
60 Maney V, Singh M (2017) An in vitro assessment of novel chitosan/bimetallic PtAu nanocomposites as delivery vehicles for doxorubicin. Nanomedicine 12:2625-2640. https://doi.org/10.2217/nnm-2017-0228   DOI
61 Quartey MO, Nyarko JNK, Pennington PR, Heistad RM, Klassen PC, Baker GB, Mousseau DD (2018) Alzheimer disease and selected risk factors disrupt a co-regulation of monoamine Oxidase-A/B in the hippocampus, but not in the cortex. Front Neurosci 12:419. https://doi.org/10.3389/fnins.2018.00419   DOI
62 Stephanou P, Konstandi M, Pappas P, Marselos M (1998) Alterations in central monoaminergic neurotrasmission induced by polycyclic aromatic hydrocarbons in rats. Eur J Drug Metab Pharmacokinet 23:475-481. https://doi.org/10.1007/BF03189998   DOI
63 Ridnour LA, Thomas DD, Mancardi D, Espey MG, Miranda KM, Paolocci N, Fukuto FM, J, Wink DA, (2004) The chemistry of nitrosative stress induced by nitric oxide and reactive nitrogen oxide species. Putting perspective on stressful biological situations. Biol Chem 385:1-10. https://doi.org/10.1515/BC.2004.001   DOI
64 Ungvari E, Monori I, Megyeri A, Csiki Z, Prokisch J, Sztrik A, Javor A, Benko I (2014) Protective effects of meat from lambs on selenium nanoparticle supplemented diet in a mouse model of polycyclic aromatic hydrocarbon-induced immunotoxicity. Food Chem Toxicol 64:298-306. https://doi.org/10.1016/j.fct.2013.12.004   DOI
65 Rodgman A, Perfetti T (2006) The composition of cigarette smoke: a catalogue of the polycyclic aromatic hydrocarbons. Beitr Tab Int Contrib Tob Res 22:13-69. https://doi.org/10.2478/cttr-2013-0817   DOI
66 Le Bihanic F, Sommard V, Perrine DL, Pichon A, Grasset J, Berrada S, Budzinski H, Cousin X, Morin B, Cachot J (2015) Environmental concentrations of benz[a]anthracene induce developmental defects and DNA damage and impair photomotor response in Japanese medaka larvae. Ecotoxicol Environ Saf 113:321-328. https://doi.org/10.1016/j.ecoenv.2014.12.011   DOI