Evaluating the Developed Model of Experimental Rhinitis in Laboratory Rats: Pre-Clinical Experimental Randomized Study

Background. Among the damaging factors affecting the mucociliary system of the nasal cavity, surgical wound is of particular relevance in the practice of an otorhinolaryngologist. The clinical assessment of regeneration of the mucociliary system is associated with certain diffi culties, since the intravital morphological examination of the nasal mucosa in patients is traumatic. Therefore, the development of animal models of experimental rhinitis is considered to be highly relevant in order to study the dynamics of mucociliary pathomorphological changes and assess the epithelium regeneration.

Objectives. To evaluate the developed model of experimental rhinitis in laboratory rats by studying clinical, morphological and biochemical changes in the infl ammatory process.

Methods. The experimental rhinitis model was developed and tested on 60 mature male Wistar rats. All animals were randomized into two groups: experimental group #1 (n = 30) — rats in which experimental rhinitis modeling was performed and group #2 (n = 30) — control, intact animals. In the course of the experiment, the authors examined the content of CRP in blood, evaluated the differential blood cell count, and studied a morphology of the nasal septum mucosa in 2, 5, 10 days after the injury to assess the dynamics of the infl ammatory process in rats of both groups. Statistical analysis of the study results was carried out by means of Statistica 8.0 (StatSoft Inc., USA).

Results. After injury, the rats from group #1 developed acute rhinitis, which was clinically manifested by the release of mucous or mucopurulent secretion from the nostrils, sneezing and scratching the nose. An increase in CRP, band and segmented neutrophils, and a decrease in lymphocytes were observed in blood of the rats from group #1 in comparison with the control group. Microscopic analysis of changes in the nasal septum mucosa showed that the acute phase of exudative infl ammation developed on the second day: vascular congestion, edema, neutrophilic infl ammatory infi ltration of the submucosal membrane were observed against the background of foci of epithelial necrosis. The proportion of lymphocytes and macrophages in the infl ammatory infi ltrate increased by the fi fth day, initial signs of restoration of epithelial tissue — the formation of an undifferentiated regenerating epithelium — appeared by the tenth day.

Conclusion. The results of the study show that an adequate experimental model of acute rhinitis in laboratory animals have been obtained. An acute infl ammatory process is characterized by clinical manifestations and changes in blood parameters. Particular destructive and reparative-proliferative changes develop in the mucous membrane of the nasal septum of experimental animals as a result of a surgical wound.

1. Kryukov A.I., Turovskiy A.B., Kolbanova I.G., Musayev K.M., Karasov A.B. Rhinitis medicamentosa — preventable disease. Medical Council. 2019; (20): 27–30 (In Russ.). DOI: 10.21518/2079-701X-2019-20-27-30

2. Svistushkin V.M., Shchennikova E.S., Sin’kov E.V., Sobolev V.P. Analysis of surgical treatment results of patients with chronic rhinitis. Medical Council. 2020; 6: 127–131 (In Russ.). DOI: 10.21518/2079-701X-2020-6-127-131

3. Vyaznikov D. A.The status of mucociliary activity of ostiomeatal complex mucous membrane in prediction of infl ammatory diseases of paranasal sinuses. Rossiiskaya Otorinolaringologiya. 2018; 1: 38–40 (In Russ.). DOI: 10.18692/1810-4800-20181-38-40

4. Beule A.G. Physiology and pathophysiology of respiratory mucosa of the nose and the paranasal sinuses. GMS Curr. Top. Otorhinolaryngol. Head. Neck. Surg. 2010; 9: Doc07. DOI: 10.3205/cto000071

5. Nosulia E.V. Medically-induced rhinitis. Vestnik Oto-Rino-Laringologii. 2017; 82(3): 84–90 (In Russ.). DOI: 10.17116/otorino201782384-90

6. Lux C.A., Douglas R.G., Cho Do-Y., Taylor M.W., Biswas K. Animal models for infl ammatory mucosal disease and their potential for studying the microbiome in chronic rhinosinusitis. Rhinology Online. 2019; 2: 69–80. DOI: 10.4193/RHINOL/19.015

7. Girkin J., Maltby S., Singanayagam A., Bartlett N., Mallia P. In vivo experimental models of infection and disease. In: Bartlett N., Wark P., Knight D. Rhinovirus Infections. Rethinking the Impact on Human Health and Disease. 2019; 195–238. DOI: 10.1016/b978-0-12-816417-4.00008-1

8. Al-Sayed A.A., Agu R.U., Massoud E. Models for the study of nasal and sinus physiology in health and disease: A review of the literature. Laryngoscope. Investig. Otolaryngol. 2017; 2(6): 398–409. DOI: 10.1002/lio2.117

9. Ostroumova O.D., Shikh E.V., Rebrova E.V., Ryazanova A.Yu. Rhinitis medicamentosa. Vestnik Oto-Rino-Laringologii. 2020; 85(3): 75–82 (In Russ.). DOI: 10.17116/otorino20208503175

10. Kryzhna S.I., Kievska Yu.A., Kozar V.V. Status of immunological resistance in experimental bacterial rinnitis and its pharmacological correction. Bulletin of Problems Biology and Medicine. 2018; 2(1(143)): 137–140 (In Ukrainian). DOI: 10.29254/20774214-2018-1-2-143-137-141

11. Day J.H., Ellis A.K., Rafeiro E., Ratz J.D., Briscoe M.P. Experimental models for the evaluation of treatment of allergic rhinitis. Ann. Allergy. Asthma. Immunol. 2006; 96(2): 263–277; quiz 277–278, 315. DOI: 10.1016/S1081-1206(10)61235-5

12. Xu J., Zhang Q., Li Z., Gao Y., Pang Z., Wu Y., Li G., Lu D., Zhang L., Li D. Astragalus Polysaccharides Attenuate Ovalbumin-Induced Allergic Rhinitis in Rats by Inhibiting NLRP3 Infl ammasome Activation and NOD2-Mediated NF-κB Activation. J. Med. Food. 2021; 24(1): 1–9. DOI: 10.1089/jmf.2020.4750

13. Altuntaş E., Yener G., Doğan R., Aksoy F., ŞerifAydın M., Karataş E. Effects of a Thermosensitive In Situ Gel Containing MometasoneFuroate on a Rat Allergic Rhinitis Model. Am. J. Rhinol. Allergy. 2018; 32(3): 132–138. DOI: 10.1177/1945892418764951

14. Chen S., Chen G., Shu S., Xu Y., Ma X. Metabolomics analysis of baicalin on ovalbumin-sensitized allergic rhinitis rats. R. Soc. Open. Sci. 2019; 6(2): 181081. DOI: 10.1098/rsos.181081

15. Köse Ş., TatlıKış T., Diniz G., Akbulut İ., GölSerin B., Yılmaz C., Özyazıcı M., Arıcı M., Yurdasiper A., Yılmaz O. A New Experimental Allergic Rhinitis Model in Mice.İzmir. Dr. Behçet. Uz. Çocuk. Hast. Dergisi. 2021; 11(3): 233–239. DOI: 10.5222/buchd.2021.86658

16. Du Q., Wang R. Effects of Biminkang mixture on AQP5 level in allergic rhinitis rats. IOP Conference Series: Earth and Environmental Science. 2021; 692(3): 032118. DOI: 10.1088/1755-1315/692/3/032118

17. Liu Z., Yang X., Liu X., Mu Y., Wang L., Song X., Zhang H. Analysis of expression of ILC2 cells in nasal mucosa based on animal model of allergic bacterial infection rhinitis. J. Infect. Public. Health. 2021; 14(1): 77–83. DOI: 10.1016/j.jiph.2019.09.010

18. Selvarajah J., Saim A.B., BtHjIdrus R., Lokanathan Y. Current and Alternative Therapies for Nasal Mucosa Injury: A Review. Int. J. Mol. Sci. 2020; 21(2): 480. DOI: 10.3390/ijms21020480

19. Čoma M., Fröhlichová L., Urban L., Zajíček R., Urban T., Szabo P., Novák Š., Fetissov V., Dvořánková B., Smetana K. Jr, Gál P. Molecular Changes Underlying Hypertrophic Scarring Following Burns Involve Specifi c Deregulations at All Wound Healing Stages (Infl ammation, Proliferation and Maturation). Int. J. Mol. Sci. 2021; 22(2): 897. DOI: 10.3390/ijms22020897

20. Khalmuratova R., Jeon S.Y., Kim D.W., Kim J.P., Ahn S.K., Park J.J., Hur D.G. Wound healing of nasal mucosa in a rat. Am. J. Rhinol. Allergy. 2009; 23(6): e33–37. DOI: 10.2500/ajra.2009.23.3390

21. El-Anwar M.W., Abdelmonem S., Abdelsameea A.A., AlShawadfy M., El-Kashishy K. The Effect of Propolis in Healing Injured Nasal Mucosa: An Experimental Study. Int. Arch. Otorhinolaryngol. 2016; 20(3): 222–225. DOI: 10.1055/s-0036-1579664

22. Choi K.Y., Cho S.W., Choi J.J., Zhang Y.L., Kim D.W., Han D.H., Kim H.J., Kim D.Y., Rhee C.S., Won T.B. Healing of the nasal septal mucosa in an experimental rabbit model of mucosal injury.World J. Otorhinolaryngol. Head Neck Surg. 2017; 3(1): 17–23. DOI: 10.1016/j.wjorl.2017.02.004

23. Kavaz E., Kurnaz S.Ç., Güvenç D., Yarım M., Aksoy A. Effects of Oral Propolis on Mucosal Wound Healing after Endoscopic Nasal Surgery in a Rabbit Model. Turk. Arch. Otorhinolaryngol. 2019; 57(2): 68–74. DOI: 10.5152/tao.2019.4164

24. Ceylan S.M., Uysal E., Sokucu M., Sezgin E., Kanmaz M.A., Yurtseven D.G., Bilal N. The Effects of Halofuginone on Wound Healing in the Rat Nasal Mucosa. Am. J. Rhinol. Allergy. 2020; 34(1): 9–15. DOI: 10.1177/1945892419866312

25. Çakan D., Uşaklıoğlu S. The effect of locally administered phenytoin on wound healing in an experimental nasal septal perforation animal model. Eur. Arch. Otorhinolaryngol. 2022; 279(7): 3511–3517. DOI: 10.1007/s00405-022-07276-z