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Short-term E-cigarette toxicity effects on brain cognitive memory functions and inflammatory responses in mice

  • Prasedya, E.S. (Faculty of Mathematics and Natural Sciences, Bioscience and Biotechnology Research Centre, University of Mataram) ;
  • Ambana, Y. (Department of Biology, Faculty of Mathematics and Natural Sciences, University of Mataram) ;
  • Martyasari, N.W.R. (Department of Pharmacy, Medical Faculty, University of Mataram) ;
  • Aprizal, Ye'muh (Department of Biology, Faculty of Mathematics and Natural Sciences, University of Mataram) ;
  • Nurrijawati, Nurrijawati (Department of Biology, Faculty of Mathematics and Natural Sciences, University of Mataram) ;
  • Sunarpi, Sunarpi (Faculty of Mathematics and Natural Sciences, Bioscience and Biotechnology Research Centre, University of Mataram)
  • Received : 2019.05.30
  • Accepted : 2019.12.06
  • Published : 2020.07.15

Abstract

Exposure to cigarette smoke (CS) is associated with an increased risk of several neurological diseases such as stroke, Alzheimer's disease, and dementia. At present, commercialization of E-cigarettes (ECs) is increasing, and they are advertised as a less harmful nicotine-delivery system. There are, however, limited studies regarding the neurotoxicity effects of ECs on the brain, which remains a subject of debate. In the present study, we aimed to evaluate the in vivo effects of short-term EC vapor exposure on the brain and compare them with the effects of cigarette smoke (CS). BALB/c mice were exposed to air, CS, and EC for 14 days. We then assessed the inflammatory responses, oxidative stress, and cognitive functions of the mice by using maze tests. Cognitive spatial tests showed that the mice exposed to CS and ECs had delayed time in finding food rewards. EC exposure demonstrated no improvement in spatial memory learning to find the food reward on the next day. This implies that CS and EC exposure possibly causes damage to the olfactory system. Notably, EC exposure potentially causes abnormalities in mice memory functions. Histological staining of the cerebral cortex of mice brain in the EC-exposed group demonstrated inflammatory responses such as necrosis and cytoplasm vacuolization. Immunohistochemical staining revealed high expression of proinflammatory cytokine TNF-α in both the EC- and CS-exposed groups. Hence, we conclude that ECs share similar toxicity profiles as CS, which potentially negatively impact brain function.

Keywords

Acknowledgement

This work was supported by an Indonesian Ministry of Research, Technology, and Higher Education grant in 2018.

References

  1. Chan YL, Saad S, Al-Odat I, Zaky AA, Oliver B, Pollock C, Li W, Jones NM, Chen H (2016) Impact of maternal cigarette smoke exposure on brain and kidney health outcomes in female offspring. Clin Exp Pharmacol Physiol 43:1168-1176 https://doi.org/10.1111/1440-1681.12659
  2. Massarsky A, Prasad GL, Di Giulio RT (2018) Total particulate matter from cigarette smoke disrupts vascular development in zebrafish brain (Danio rerio). Toxicol Appl Pharmacol 339:85-96 https://doi.org/10.1016/j.taap.2017.12.003
  3. Yuan M, Cross SJ, Loughlin SE, Leslie FM (2015) Nicotine and the adolescent brain. J Physiol 593:3397-3412 https://doi.org/10.1113/JP270492
  4. Mendrek A, Monterosso J, Simon SL, Jarvik M, Brody A, Olmstead R, Domier CP, Cohen MS, Ernst M, London ED (2006) Working memory in cigarette smokers: comparison to nonsmokers and effects of abstinence. Addict Behav 31:833-844 https://doi.org/10.1016/j.addbeh.2005.06.009
  5. Bashir S, Alghamd F, Alhussien A, Alohali M, Alatawi A, Almusned T, Habib SS (2017) Effect of smoking on cognitive functioning in young saudi adults. Med Sci Monit Basic Res 23:31-35 https://doi.org/10.12659/MSMBR.902385
  6. Hong JS, Kim SM, Jung HY, Kang KD, Min KJ, Han DH (2017) Cognitive avoidance and aversive cues related to tobacco in male smokers. Addict Behav 73:158-164 https://doi.org/10.1016/j.addbeh.2017.05.003
  7. Zhong G, Wang Y, Zhang Y, Guo JJ, Zhao Y (2015) Smoking is associated with an increased risk of dementia: a meta-analysis of prospective cohort studies with investigation of potential effect modifers. PLoS ONE 10:e0118333 https://doi.org/10.1371/journal.pone.0118333
  8. Durazzo TC, Korecka M, Trojanowski JQ, Weiner MW, O'Hara R, Ashford JW, Shaw LM, Alzheimer's Disease Neuroimaging Initiative (2016) Active cigarette smoking in cognitively-normal elders and probable alzheimer's disease is associated with elevated cerebrospinal fluid oxidative stress biomarkers. J Alzheimers Dis 54:99-107
  9. Toda N, Okamura T (2016) Cigarette smoking impairs nitric oxide-mediated cerebral blood flow increase: implications for Alzheimer's disease. J Pharmacol Sci 131:223-232 https://doi.org/10.1016/j.jphs.2016.07.001
  10. Levy DT, Yuan Z, Li Y (2017) The prevalence and characteristics of E-cigarette users in the U.S. Int J Environ Res Public Health 14:E1200. https://doi.org/10.3390/ijerph14101200
  11. Bold KW, Kong G, Cavallo DA, Camenga DR, Krishnan-Sarin S (2017) E-cigarette susceptibility as a predictor of youth initiation of E-cigarettes. Nicotine Tob Res 20:140-144
  12. Sears CG, Hart JL, Walker KL, Robertson RM (2017) Generally recognized as safe: uncertainty surrounding E-cigarette flavoring safety. Int J Environ Res Public Health 14
  13. Rom O, Pecorelli A, Valacchi G, Reznick AZ (2015) Are E-cigarettes a safe and good alternative to cigarette smoking? Ann N Y Acad Sci 1340:65-74
  14. Simmons VN, Quinn GP, Harrell PT, Meltzer LR, Correa JB, Unrod M, Brandon TH (2016) E-cigarette use in adults: a qualitative study of users' perceptions and future use intentions. Addict Res Theory 24:313-321
  15. Hughes A, Hendrickson RG (2019) An epidemiologic and clinical description of e-cigarette toxicity. Clin Toxicol (Phila) 57:287-293 https://doi.org/10.1080/15563650.2018.1510503
  16. Bengalli R, Ferri E, Labra M, Mantecca P (2017) Lung toxicity of condensed aerosol from E-CIG liquids: influence of the flavor and the in vitro model used. Int J Environ Res Public Health 14
  17. Payne JD, Michaels D, Orellana-Barrios M, Nugent K (2017) Electronic cigarette toxicity. J Prim Care Community Health 8:100-102 https://doi.org/10.1177/2150131916668645
  18. Sancilio S, Gallorini M, Cataldi A, Sancillo L, Rana RA, di Giacomo V (2017) Modifications in human oral fibroblast ultras-tructure, collagen production, and lysosomal compartment in response to electronic cigarette fluids. J Periodontol 88:673-680 https://doi.org/10.1902/jop.2017.160629
  19. Ghosh A, Coakley RC, Mascenik T, Rowell TR, Davis ES, Rogers K, Webster MJ, Dang H, Herring LE, Sassano MF et al (2018) Chronic E-cigarette exposure alters the human bronchial epithelial proteome. Am J Respir Crit Care Med 198:67-76 https://doi.org/10.1164/rccm.201710-2033oc
  20. Aug A, Altraja S, Kilk K, Porosk R, Soomets U, Altraja A (2015) E-cigarette affects the metabolome of primary normal human bronchial epithelial cells. PLoS ONE 10:e0142053 https://doi.org/10.1371/journal.pone.0142053
  21. Lappas AS, Tzortzi AS, Konstantinidi EM, Teloniatis SI, Tzavara CK, Gennimata SA, Koulouris NG, Behrakis PK (2018) Shortterm respiratory effects of e-cigarettes in healthy individuals and smokers with asthma. Respirology 23:291-297
  22. Clapp PW, Jaspers I (2017) Electronic cigarettes: their constituents and potential links to asthma. Curr Allergy Asthma Rep 17:79 https://doi.org/10.1007/s11882-017-0747-5
  23. Sussan TE, Gajghate S, Thimmulappa RK, Ma J, Kim JH, Sudini K, Consolini N, Cormier SA, Lomnicki S, Hasan F et al (2015) Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model. PLoS ONE 10
  24. Neal RE, Jagadapillai R, Chen J, Webb C, Stocke K, Greene RM, Pisano MM (2016) Developmental cigarette smoke exposure II: hippocampus proteome and metabolome profiles in adult offspring. Reprod Toxicol 65:436-447
  25. Quiroz-Padilla MF, Guillazo-Blanch G, Vale-Martinez A, MartiNicolovius M (2006) Excitotoxic lesions of the parafascicular nucleus produce deficits in a socially transmitted food preference. Neurobiol Learn Mem 86:256-263 https://doi.org/10.1016/j.nlm.2006.03.007
  26. Cardiff RD, Miller CH, Munn RJ (2014) Manual immunohistochemistry staining of mouse tissues using the avidin-biotin complex (ABC) technique. Cold Spring Harb Protoc 2014:659-662
  27. Katotomichelakis M, Balatsouras D, Tripsianis G, Davris S, Maroudias N, Danielides V, Simopoulos C (2007) The effect of smoking on the olfactory function. Rhinology 45:273-280
  28. Onor IO, Stirling DL, Williams SR, Bediako D, Borghol A, Harris MB, Darensburg TB, Clay SD, Okpechi SC, Sarpong DF (2017) Clinical effects of cigarette smoking: epidemiologic impact and review of pharmacotherapy options. Int J Environ Res Public Health 14
  29. Glasser AM, Katz L, Pearson JL, Abudayyeh H, Niaura RS, Abrams DB, Villanti AC (2017) Overview of electronic nicotine delivery systems: a systematic review. Am J Prev Med 52:e33-e66 https://doi.org/10.1016/j.amepre.2016.10.036
  30. Salamanca JC, Meehan-Atrash J, Vreeke S, Escobedo JO, Peyton DH, Strongin RM (2018) E-cigarettes can emit formaldehyde at high levels under conditions that have been reported to be nonaverse to users. Sci Rep 8
  31. Jitnarin N, Kosulwat V, Rojroongwasinkul N, Boonpraderm A, Haddock CK, Poston WSC (2014) The relationship between smoking, body weight, body mass index, and dietary intake among Thai adults: results of the national Thai food consumption survey. Asia Pac J Public Health 26:481-493 https://doi.org/10.1177/1010539511426473
  32. Audrain-McGovern J, Benowitz N (2011) Cigarette smoking, nicotine, and body weight. Clin Pharmacol Ther 90:164-168
  33. Dare S, Mackay DF, Pell JP (2015) Relationship between smoking and obesity: a cross-sectional study of 499,504 middle-aged adults in the UK general population. PLoS ONE 10
  34. Aubin HJ, Farley A, Lycett D, Lahmek P, Aveyard P (2012) Weight gain in smokers after quitting cigarettes: meta-analysis. BMJ 345
  35. Mangubat M, Lutfy K, Lee ML, Pulido L, Stout D, Davis R, Shin C-S, Shahbazian M, Seasholtz S, Sinha-Hikim A et al (2012) Effect of nicotine on body composition in mice. J Endocrinol 212:317-326 https://doi.org/10.1530/JOE-11-0350
  36. Kalmijn S, van Boxtel MPJ, Verschuren MWM, Jolles J, Launer LJ (2002) Cigarette smoking and alcohol consumption in relation to cognitive performance in middle age. Am J Epidemiol 156:936-944 https://doi.org/10.1093/aje/kwf135
  37. Starr JM, Deary IJ, Fox HC, Whalley LJ (2007) Smoking and cognitive change from age 11 to 66 years: a confirmatory investigation. Addict Behav 32:63-68 https://doi.org/10.1016/j.addbeh.2006.03.020
  38. Omotoso GO, Babalola FA (2014) Histological changes in the cerebelli of adult wistar rats exposed to cigarette smoke. Niger J Physiol Sci 29:43-46
  39. Jacobus J, Squeglia LM, Sorg SF, Nguyen-Louie TT, Tapert SF (2014) Cortical thickness and neurocognition in adolescent marijuana and alcohol users following 28 days of monitored abstinence. J Stud Alcohol Drugs 75:729-743
  40. Bryant VE, Kahler CW, Devlin KN, Monti PM, Cohen RA (2013) The effects of cigarette smoking on learning and memory performance among people living with HIV/AIDS. AIDS Care 25:1308-1316 https://doi.org/10.1080/09540121.2013.764965
  41. Liu J-T, Lee I-H, Wang C-H, Chen K-C, Lee C-I, Yang Y-K (2013) Cigarette smoking might impair memory and sleep quality. J Formos Med Assoc 112:287-290 https://doi.org/10.1016/j.jfma.2011.12.006
  42. Sartori AC, Vance DE, Slater LZ, Crowe M (2012) The impact of inflammation on cognitive function in older adults: implications for health care practice and research. J Neurosci Nurs 44:206-217 https://doi.org/10.1097/JNN.0b013e3182527690
  43. Zhang L, Spencer TJ, Biederman J, Bhide PG (2018) Attention and working memory deficits in a perinatal nicotine exposure mouse model. PLoS ONE 13:e0198064 https://doi.org/10.1371/journal.pone.0198064
  44. Kukull WA (2001) The association between smoking and Alzheimer's disease: effects of study design and bias. Biol Psychiat 49:194-199 https://doi.org/10.1016/S0006-3223(00)01077-5
  45. Corley J, Gow AJ, Starr JM, Deary IJ (2012) Smoking, childhood IQ, and cognitive function in old age. J Psychosom Res 73:132-138 https://doi.org/10.1016/j.jpsychores.2012.03.006
  46. Ponzoni L, Moretti M, Sala M, Fasoli F, Mucchietto V, Lucini V, Cannazza G, Gallesi G, Castellana CN, Clementi F, Zoli M, Gotti C, Braida D (2015) Different physiological and behavioural effects of e-cigarette vapour and cigarette smoke in mice. Eur Neuropsychopharmacol 25:1775-1786 https://doi.org/10.1016/j.euroneuro.2015.06.010
  47. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L (2017) Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 9:7204-7218 https://doi.org/10.18632/oncotarget.23208
  48. Peila R, Launer LJ (2006) Inflammation and dementia: epidemiologic evidence. Acta Neurol Scand Suppl 185:102-106
  49. Hart J (2002) Inflammation. 1: its role in the healing of acute wounds. J Wound Care 11:205-209 https://doi.org/10.12968/jowc.2002.11.6.26411
  50. Wilson CB, McLaughlin LD, Nair A, Ebenezer PJ, Dange R, Francis J (2013) Inflammation and oxidative stress are elevated in the brain, blood, and adrenal glands during the progression of posttraumatic stress disorder in a predator exposure animal model. PLoS ONE 8:e76146 https://doi.org/10.1371/journal.pone.0076146
  51. Rock KL, Kono H (2008) The infiammatory response to cell death. Annu Rev Pathol 3:99-126 https://doi.org/10.1146/annurev.pathmechdis.3.121806.151456
  52. Yang Y, Jiang G, Zhang P, Fan J (2015) Programmed cell death and its role in inflammation. Mil Med Res 2
  53. Shubin AV, Demidyuk IV, Komissarov AA, Rafieva LM, Kostrov SV (2016) Cytoplasmic vacuolization in cell death and survival. Oncotarget 7:55863-55889 https://doi.org/10.18632/oncotarget.10150
  54. Petrescu F, Voican SC, Silosi I (2010) Tumor necrosis factor-α serum levels in healthy smokers and nonsmokers. Int J Chron Obstruct Pulmon Dis 5:217-222
  55. Tanni SE, Pelegrino NR, Angeleli AY, Correa C, Godoy I (2010) Smoking status and tumor necrosis factor-alpha mediated systemic inflammation in COPD patients. J Inflamm (Lond) 7:29 https://doi.org/10.1186/1476-9255-7-29
  56. Yafe K, Lindquist K, Penninx BW, Simonsick EM, Pahor M, Kritchevsky S, Launer L, Kuller L, Rubin S, Harris T (2003) Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology 61:76-80
  57. Abramson JL, Vaccarino V (2002) Relationship between physical activity and inflammation among apparently healthy middle-aged and older US adults. Arch Intern Med 162:1286-1292 https://doi.org/10.1001/archinte.162.11.1286

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