Type of Article:  Original Research

Volume 7; Issue 2.2 (May 2019)

Page No.: 6581-6589

DOI: https://dx.doi.org/10.16965/ijar.2019.174


Nehal Mohamed Nabil *1, Samar El Achy 2.

*1 Anatomy and Embryology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

2 Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

Correspondence Author: Nehal Mohamed Nabil, Anatomy and Embryology department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.  E-Mail: nehalnabil895@gmail.com


Background: Zinc oxide nanoparticles (ZnO-NPs) are frequently used in many fields, including food industry for their antimicrobial activity. Acute exposure to high doses of such particles was found to be toxic to many organs. However, the lung toxicity resulting from chronic exposure to oral doses of ZnO-NPs was not adequately assessed before.

Aim of the work: to detect the anatomical and histopathological effects of chronic exposure to ingested ZnO-NPs on the lung of normal adult male albino rat.

Material and methods: It was carried out on 30 adult male Swiss albino rats with an average weight of 150-200 gm. They were divided into two groups: Group I: 10 rats serving as control group; Group II: 20 rats serving as experimental groups, divided into 2 subgroups (a&b) receiving oral ingestion by orogastric tube of a single daily dose (125mg/ kg) of average 20 nm sized ZnO-NPs for different durations: Group IIa (n=10):  for 120 days; Group IIb (n=10): for 180 days. Histopathology and immunohistochemistry of the lungs in the three groups was performed to detect the possible effect of such exposure.

Results: Oral administration of ZnO-NPs induced lung damage manifested by congested blood vessels, interstitial inflammation, infiltration with macrophages& lymphocytes, supurative granuloma, thickened interalveolar septa. These changes were more evident with longer exposure for 180 days (P≤0.5). This substantial damage to the lungs is caused by oxidative stress and chronic inflammation.

Conclusion: Caution should be considered when using these particles in food packaging and food additives, and for those who are in close contact with these particles especially in factories.

Key words: ZnO-NPs, Oral ingestion, Immunohistochemistry, lungs.


  1. Rashidi L, Khosravi-Darani K. The applications of nanotechnology in food industry. Crit Rev Food Sci Nutr 2011; 51(8):723–730.
  2. Clarence SY, Geoffrey SS, Sunny EI. Nanoparticles toxicity and their routes of exposure. Pak J Pharm Sci 2012; 25(2):477–491.
  3. Matsuyama K, Ihsan N, Irie K, Mishima K, Okuyama T, Muto H. Bioimaging application of highly luminescent silica-coated ZnOnanoparticle quantum dots with biotin. J Colloid Interface Sci  2013; 399:19-25.
  4. Jin T, Sun D, Su JY, Zhang H, Sue HJ. Antimicrobial efficacy of zinc oxide quantum dots against Listeria monocytogenes, Salmonella Enteritidis, and Escherichia coli O157:H7. J Food Sci 2009; 74(1): M46–M52.
  5. Lu, S.; Zhang, W.; Zhang, R.; Liu, P.; Wang, Q.; Shang, Y.; Wu, M.; Donaldson, K.; Wang, Q. Comparison of cellular toxicity caused by ambient ultrafine particles and engineered metal oxide nanoparticles. Part Fibre Toxicol 2015; 12 :5 .
  6. Sharma V, Singh P, Pandey AK, Dhawan A. Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles. Mutat Res 2012; 745: 84-91.
  7. Vandebriel RJ and De Jong WH. A review of mammalian toxicity of ZnO nanoparticles. Nanotechnol. Sci. Applic  2012; 5: 61-71.
  8. Ghorbani M., Soheili S. Moradhaseli S, and Shokouhian A. Histopathological effects of ZnO nanoparticles on liver and heart tissues in wistar rats. Adv. Biores 2013; 4: 83-88.
  9. [9].             Park HS, Kim SJ, Lee TJ, Kim GY, Meang E, Hong JS, et al. A 90-day study of sub  chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats. Int J Nanomedicine  2014; 9 (Suppl 2): 93–107.
  10. Ko JW, Hong ET, Lee IC, Park SH, Park JI, Seong NW, et al. Evaluation of 2-week repeated oral dose toxicity of 100 nm zinc oxide nanoparticles in rats. Lab Anim Res  2015; 31(3):139-47.
  11. Cho WS, Duffin R, Howie SE, Scotton CJ, Wallace WA, Macnee W, et al. Progressive severe lung injury by zinc oxide nanoparticles;the role of Zn2+ dissolution inside lysosomes. Part Fibre Toxicol  2011; 8: 27.
  12. Shokouhian A, Soheili S, Moradhaseli S, Fazli L, Ardestani MS, and Masoud Ghorbani . Toxicity of zinc oxide nanoparticles in lung tissue after repeated oral administration. American Journal of Pharmacology and Toxicology 2013; 8 (4): 148-154.
  13. Jain S, Rachamalla M, Kulkarni A, Kaur J, Tikoo K. Pulmonary fibrotic response to inhalation of ZnO nanoparticles and toluene co-exposure through directed flow nose only exposure chamber. Inhal Toxicol. 2013 ; 25(13):703-713.
  14. Morimoto Y, Izumi H, Yoshiura Y, Tomonaga T, Oyabu T, Myojo T, et al. Evaluation of Pulmonary Toxicity of ZincOxide Nanoparticles Following Inhalation and Intratracheal Instillation. Int J Mol Sci  2016; 17(8): E1241.
  15. Yoo J, Seo GB. , Yoon BI. , Lim YM, Kim P, Kim HM , Kwon JT. Evaluation of recovery from acute lung injury induced by intratracheal instillation of zinc oxide nanoparticles. Applied ecology and environmental research 2018; 16(3):3145-3157.
  16. Mahato TH, Prasad GK , Singh BJ, Acharya J, Srivastava AR, Vijayaraghavan R. Nanocrystalline zinc oxide for the decontamination of sarin. Journal of Hazardous Materials 2009; 165: 928–932.
  17. Suryanarayana C, Norton M G. X- ray Diffraction: A practical approach (Artech House Telecommunications) New York: Plenum Press; 1998. P. 63-96.
  18. Waseda Y, Muramatsu A. Morphology control of materials and nanoparticles: Advanced materials processing and characterization. Berlin: Springer; 2004. P. 85-87.
  19. Eidi H , Joubert O, Nemos C, Grandemange S, Mograbi B, Foliguet B, et al. Drug delivery by polymeric nanoparticles induces autophagy in macrophages. Int J Pharm 2012; 422 (1): 495-503.
  20. Hosokawa M, Nogi K, Naito M, Yokoyama T. Nanoparticle technology hand book. 2nd ed. Amesterdam: Elsevier; 2012, P. 5-51.
  21. El Morshedi N, AlZahrani I, Kizilbash NA, AlFayez HA. Toxic effect of Zinc Oxide Nanoparticles on some organs in Experimental Male Wister Rats. IJAR 2014; 2 (4): 907-915.
  22. Chung HE, Yu J , Baek M, Lee JA, Kim MS, Kim SH, et al. Toxicokinetics of zinc oxide nanoparticles in rats. J Phs Conf Ser  2013; 429; 012037.
  23. Bai D P, Zhang X F, Zhang G L, Huang Y F, and Gurunathan S. Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells. Int. J. Nanomed 2017;12: 6521–6535.
  24. Fukui H, Iwahashi H, Nishio K, Hagihara Y, Yoshida Y, Horie M. Ascorbic acid prevents zinc oxide nanoparticle-induced intracellular oxidative stress and inflammatory responses. Toxicol Ind Health  2017; 33(9):687-695.
  25. Byers DE, and Holtzman MJ. Alternatively activated macrophages and airway disease. Chest 2011; 140:768–774.
  26. Nemmar A, Al-Salam S, Beegam S, Yuvaraju P, Ali BH. The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intra-tracheal instillation in mice. Int J Nanomedicine. 2017; 12: 2913- 2922.
  27. Qiao Y, Liang X, Yan Y, Lu Y, Zhang D, Yao W, et al. Identification of Exosomal miRNAs in Rats With Pulmonary Neutrophilic Inflammation Induced by Zinc Oxide Nanoparticles.   Physiol  2018; 9:217.

Cite this article: Nehal Mohamed Nabil, Samar El Achy. ANATOMICAL AND HISTOPATHOLOGICAL EFFECTS OF ZINC OXIDE NANOPARTICLES ON LUNGS IN ADULT MALE ALBINO RATS. Int J Anat Res 2019;7(2.2):6581-6589. DOI: 10.16965/ijar.2019.174