ORIGINAL RESEARCH
The Potential Anti-Inflammatory Effects of Naringenin on a Histamin Induced Otitis Media with Efussion Rat Model
Histamin ile Oluşturulmuş Efüzyonlu Otitis Media Rat Modelinde Naringeninin Potansiyel Antiinflamatuar Etkileri
Received Date : 05 Jul 2023
Accepted Date : 01 Sep 2023
Available Online : 08 Sep 2023
Mustafa İBASa, Necmi ARSLANa, Ramazan ÖÇALa, Songül DURSUNb, Nihat YUMUŞAKc, Rahmi KILIÇa
aDepartment of Otorhinolaryngology, Head and Neck Surgery, University of Health Sciences Ankara Training and Research Hospital, Ankara, Türkiye
bDepartment of Otorhinolaryngology, Head and Neck Surgery, İstanbul Surgery Hospital, İstanbul, Türkiye
cDepartment of Pathology, Harran University Faculty of Veterinary Medicine, Şanlıurfa, Türkiye
Doi: 10.24179/kbbbbc.2023-98723 - Makale Dili: EN
Journal of Ear Nose Throat and Head Neck Surgery. 2023;31(4):206-13.
Copyright © 2020 by Turkey Association of Society of Ear Nose Throat and Head Neck Surgery. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
ABSTRACT
Objective: The aim of this study was to histopathologically
compare the effects of naringenin with methyl-prednisolone (MP)
on a histamine induced otitis media with effusion (OME) animal model.
Material and Methods: Twenty seven male Albino Wistar rats weighing
250-300 g were used in this study. A histamine induced OME
model was created by trans-tympanic 0.2 mL injections of 1 mg/mL
histamine in both ears in all rats. Three groups of 9 rats were formed by
a random selection. Group 1 did not receive any treatment, Group 2 received
1 mg/kg of intra-peritoneal MP treatment for 14 days and Group
3 received 50 mg/kg oral naringenin treatment. All rats were otomicroscopically
examined on the 48th hour in order to confirm the development
of OME. At the end of the treatment, all rats were
otomicroscopically re-examined and later sacrificed. The temporal bulla
of all rats was examined with light microscopy and was evaluated in
terms of submucosal neutrophil leucocyte count. Results: The first otomicroscopic
evaluation revealed that 52 ears of 26 rats developed OME
(96%). In the second oto-microscopic evaluation, OME was present in
16 ears (88%) in Group 1, 3 ears (19%) in Group 2 and 7 ears (39%) in
Group 3. In terms of submucosal neutrophil count statistically significant
difference was present between Group 1 and Group 2 and 3
(p<0.05) however no significant difference was present between Group
2 and 3 (p=0.21). Conclusion: Naringenin was found as effective as
MP in both oto-microscopical examinations and histopathological evaluations
in a histamine induced animal model of OME.
Keywords: Otitis media with effusion; naringenin; methyl-prednisolone
ÖZET
Amaç: Bu çalışmanın amacı, histamin ile oluşturulmuş deneysel
efüzyonlu otitis media (EOM) hayvan modelinde naringenin ve
metil-prednizolonun etkilerini histolojik olarak karşılaştırmaktır. Gereç
ve Yöntemler: Bu çalışmada, ağırlıkları 250-300 g olan 27 adet erkek
Albino Wistar ratları kullanıldı. Tüm ratlarda her iki kulağa transtimpanik
0,2 mL 1 mg/mL histamin enjeksiyonu ile EOM modeli oluşturuldu.
Rastgele seçimle 9 rattan oluşan 3 grup oluşturuldu. Grup 1’e
herhangi bir tedavi uygulanmadı, Grup 2’ye 14 gün 1 mg/kg intraperitoneal
metil-prednizolon tedavisi ve Grup 3’e 50 mg/kg oral naringenin
tedavisi verildi. EOM gelişimini doğrulamak için tüm sıçanlar 48.
saatte otomikroskopik olarak incelendi. Tedavi sonunda tüm sıçanlar
otomikroskopik olarak tekrar incelendi ve daha sonra sakrifiye edildi.
Tüm sıçanların temporal bullası ışık mikroskobu ile incelendi ve submukozal
nötrofil lökosit sayısı açısından değerlendirildi. Bulgular: İlk
otomikroskopik değerlendirmede, 26 ratın 52 (%96) kulağında EOM
geliştiği görüldü. İkinci otomikroskopik değerlendirmede, Grup 1’de
16 kulakta (%88), Grup 2’de 3 kulakta (%19), Grup 3’te 7 kulakta
(%39) EOM mevcuttu. Submukozal nötrofil sayısı açısından Grup 1
ile Grup 2 ve 3 arasında istatistiksel olarak anlamlı fark vardı (p<0,05),
ancak Grup 2 ile 3 arasında anlamlı fark yoktu (p=0,21). Sonuç: Histamin
ile oluşturulan EOM hayvan modelinde hem otomikroskopik incelemelerde
hem de histopatolojik değerlendirmelerde naringenin, MP
kadar etkili bulunmuştur.
Anahtar Kelimeler: Efüzyonlu otitis media; naringenin; metil-prednizolon
KAYNAKLAR
- Simon F, Haggard M, Rosenfeld RM, Jia H, Peer S, Calmels MN, et al. International consensus (ICON) on management of otitis media with effusion in children. Eur Ann Otorhinolaryngol Head Neck Dis. 2018;135(1S):S33-S9. [Crossref] [PubMed]
- Tos M. Epidemiology and natural history of secretory otitis. Am J Otol. 1984;5(6):459-62. [PubMed]
- Williamson IG, Dunleavey J, Bain J, Robinson D. The natural history of otitis media with effusion-a three-year study of the incidence and prevalence of abnormal tympanograms in four South West Hampshire infant and first schools. J Laryngol Otol. 1994;108(11):930-4. [Crossref] [PubMed]
- Marchant CD, Shurin PA, Turczyk VA, Wasikowski DE, Tutihasi MA, Kinney SE. Course and outcome of otitis media in early infancy: a prospective study. J Pediatr. 1984;104(6):826-31. [Crossref] [PubMed]
- Atkinson H, Wallis S, Coatesworth AP. Otitis media with effusion. Postgrad Med. 2015;127(4):381-5. [Crossref] [PubMed]
- Rosenfeld RM, Shin JJ, Schwartz SR, Coggins R, Gagnon L, Hackell JM, et al. Clinical practice guideline: otitis media with effusion executive summary (Update). Otolaryngol Head Neck Surg. 2016;154(2):201-14. [Crossref] [PubMed]
- American Academy of Family Physicians; American Academy of Otolaryngology-Head and Neck Surgery; American Academy of Pediatrics Subcommittee on Otitis Media With Effusion. Otitis media with effusion. Pediatrics. 2004;113(5):1412-29. [Crossref] [PubMed]
- Arafah A, Rehman MU, Mir TM, Wali AF, Ali R, Qamar W, et al. Multi-therapeutic potential of naringenin (4',5,7-trihydroxyflavonone): experimental evidence and mechanisms. Plants (Basel). 2020;9(12):1784. [Crossref] [PubMed] [PMC]
- Vanneste P, Page C. Otitis media with effusion in children: Pathophysiology, diagnosis, and treatment. A review. J Otol. 2019;14(2):33-9. [Crossref] [PubMed] [PMC]
- Chung MH, Choi JY, Lee WS, Kim HN, Yoon JH. Compositional difference in middle ear effusion: mucous versus serous. Laryngoscope. 2002;112(1):152-5. [Crossref] [PubMed]
- Berger G, Hawke M, Proops DW, Ranadive NS, Wong D. Histamine levels in middle ear effusions. Acta Otolaryngol. 1984;98(5-6):385-90. [Crossref] [PubMed]
- Kaytez SK, Ocal R, Yumusak N, Celik H, Arslan N, Ibas M. Effect of probiotics in experimental otitis media with effusion. Int J Pediatr Otorhinolaryngol. 2020;132:109922. [Crossref] [PubMed]
- Aynali G, Yariktaş M, Yasan H, Karahan N, Başpinar S, Tüz M, et al. The effects of methylprednisolone, montelukast and indomethacine in experimental otitis media with effusion. Int J Pediatr Otorhinolaryngol. 2011;75(1):15-9. [Crossref] [PubMed]
- Yaman H, Ozturk K, Uyar Y, Gurbilek M. Effectiveness of corticosteroids in otitis media with effusion: an experimental study. J Laryngol Otol. 2008;122(1):25-30. [Crossref] [PubMed]
- Rosenfeld RM, Mandel EM, Bluestone CD. Systemic steroids for otitis media with effusion in children. Arch Otolaryngol Head Neck Surg. 1991;117(9):984-9. [Crossref] [PubMed]
- Roditi RE, Rosenfeld RM, Shin JJ. Otitis Media with Effusion: Our National Practice. Otolaryngol Head Neck Surg. 2017;157(2):171-2. [Crossref] [PubMed]
- Cengel S, Akyol MU. The role of topical nasal steroids in the treatment of children with otitis media with effusion and/or adenoid hypertrophy. Int J Pediatr Otorhinolaryngol. 2006;70(4):639-45. [Crossref] [PubMed]
- Williamson I, Benge S, Barton S, Petrou S, Letley L, Fasey N, et al. A double-blind randomised placebo-controlled trial of topical intranasal corticosteroids in 4- to 11-year-old children with persistent bilateral otitis media with effusion in primary care. Health Technol Assess. 2009;13(37):1-144. [Crossref] [PubMed]
- Kozan G, Aktan B, Sakat MS, Kurt S, Öner F, Kara A. Effect of systemic clarithromycin and prednisolone on histamine-induced otitis media in guinea pigs. Acta Otolaryngol. 2015;135(10):978-84. [Crossref] [PubMed]
- Ucuncu H, Aktan B, Ozabacigil F, Buyukokuroglu ME, Akyuz M, Altas E. Protective effect of melatonin on experimental otitis media with effusion in guinea pigs. Ann Clin Lab Sci. 2004;34(3):341-6. [PubMed]
- Fan R, Pan T, Zhu AL, Zhang MH. Anti-inflammatory and anti-arthritic properties of naringenin via attenuation of NF-κB and activation of the heme oxygenase ﴾HO﴿-1/related factor 2 pathway. Pharmacol Rep. 2017;69(5):1021-9. [Crossref] [PubMed]
- Şahin A, Sakat MS, Kılıç K, Aktan B, Yildirim S, Kandemir FM, et al. The protective effect of Naringenin against ovalbumin-induced allergic rhinitis in rats. Eur Arch Otorhinolaryngol. 2021;278(12):4839-46. [Crossref] [PubMed]
- Pudrith C, Kim YH, Martin D, Gupta A, Inman J, Wareham R, et al. Effect of topical glucocorticoid treatment in chinchilla model of lipopolysaccharide induced otitis media with effusion. Int J Pediatr Otorhinolaryngol. 2010;74(11):1273-5. [Crossref] [PubMed]
- MacArthur CJ, DeGagne JM, Kempton JB, Trune DR. Steroid control of acute middle ear inflammation in a mouse model. Arch Otolaryngol Head Neck Surg. 2009;135(5):453-7. [Crossref] [PubMed] [PMC]
- Jayaraman J, Jesudoss VA, Menon VP, Namasivayam N. Anti-inflammatory role of naringenin in rats with ethanol induced liver injury. Toxicol Mech Methods. 2012;22(7):568-76. [Crossref] [PubMed]
- Hernández-Aquino E, Muriel P. Beneficial effects of naringenin in liver diseases: Molecular mechanisms. World J Gastroenterol. 2018;24(16):1679-707. [Crossref] [PubMed] [PMC]
- Cavia-Saiz M, Busto MD, Pilar-Izquierdo MC, Ortega N, Perez-Mateos M, Mu-iz P. Antioxidant properties, radical scavenging activity and biomolecule protection capacity of flavonoid naringenin and its glycoside naringin: a comparative study. J Sci Food Agric. 2010;90(7):1238-44. [Crossref] [PubMed]
- Sekiyama K, Ohori J, Matsune S, Kurono Y. The role of vascular endothelial growth factor in pediatric otitis media with effusion. Auris Nasus Larynx. 2011;38(3):319-24. [Crossref] [PubMed]
- Pafumi I, Festa M, Papacci F, Lagostena L, Giunta C, Gutla V, et al. Naringenin impairs two-pore channel 2 activity and inhibits VEGF-induced angiogenesis. Sci Rep. 2017;7(1):5121. [Crossref] [PubMed] [PMC]
- Tutunchi H, Naeini F, Ostadrahimi A, Hosseinzadeh-Attar MJ. Naringenin, a flavanone with antiviral and anti-inflammatory effects: A promising treatment strategy against COVID-19. Phytother Res. 2020;34(12):3137-47. [Crossref] [PubMed] [PMC]
