The Effect of Thymoquinone on Experimental Model of Allergic Conjunctivitis

Year 2020, , 17 - 22, 12.01.2020

Tolga Kocatürk Ayşe İpek Akyüz Ünsal , Ceren Günel , Buket Demirci , İbrahim Meteoğlu Harun Çakmak , İmran Kurt Ömürlü

https://doi.org/10.30934/kusbed.596688

Cited By: 1

Abstract

Objective: Treatment
of allergic conjunctivitis is challenging and new treatment modalities are
required. In this study; the effect of Thymoquinone (TK), a natural derivative
of Nigella Sativa with its anti-allergic and anti-inflammatory properties, was
investigated on an experimental rat model of allergic conjunctivitis (AK). 

Methods: Forty-eight
female Wistar Albino rats aging between 4-6 months were included in this study.
Rats were divided into 6 groups as following: control, AK, AK + Dexamethasone,
10 mg/kg TK, AK + 3 mg/kg TK and AK + 10 mg/kg TK. To induce an AK rat model,
Ovalbumin (0.3 mg) and Al(OH)₃ (30 mg/ml) in 1 ml of %0.9 NaCl were
given 7 times intraperitoneally (i.p.) to each rat every other day. Ovalbumin
drops (2%) were installed everyday between 15^th-21^th days
directly on conjunctiva. TK was applied i.p. with above mentioned doses. Tissue
Mast Cell Counts (MCC) and histopathological - immunohistochemical staining
results were statistically evaluated.

Results:
Systemic administration of Thymoquinone
alone did not demonstrate any detrimental effect on eye tissues. MCC of
Ovallbumin sensitized AK group was significantly higher than the control cases
(p<0.001). Similar to dexamethasone treated group (p<0.001),
MCC of TK treated group was lower than AK groups’, but the difference was not
statistically significant. As a common finding in all treatment groups weak
focal TGF-β staining and negative TNF-α staining have been determined.

Conclusion: Administration of Ovalbumin using
aforementioned way creates a proper AK
model. TK is a safe non-allergic herbal product and may have a
supplementary role in AK treatment by its anti-inflammatory effect but
unfortunately, it has not reached remarkable anti-allergic effect.

Keywords

Allergic Conjunctivitis model, Nigella Sativa, Thymoquinone

Deneysel Alerjik Konjonktivit Modelinde Çörek Otu Bileşenlerinden Timokinon'un Etkisi

Abstract

Amaç: Alerjik konjonktivit
tedavisi güç bir hastalıktır; yeni tedavi seçeneklerine ihtiyaç vardır. Bu
çalışmada anti-inflamatuar ve anti-alerjik özellikleri olan ve çörek otundan
(Nigella Sativa) elde edilen timokinonun (TK) sıçan alerjik konjonktivit (AK)
modeli üzerindeki etkisinin histolojik yöntemlerle araştırılması amaçlanmıştır.

Yöntem: Çalışmaya 48 adet 4-6 aylık yetişkin Wistar Albino
dişi sıçan dahil edildi. Sıçanlar; kontrol, AK, AK+Deksametazon, 10 mg/kg TK,
AK+3 mg/kg TK ve AK+10 mg/kg TK şeklinde rastgele 6 gruba ayrıldı. AK
geliştirmek için, 30 mg/ml adjuvan Al(OH)₃  ve 0,3 mg
Ovalbumin, serum fizyolojik içinde her sıçana 1 mL intraperitoneal (i.p.)
olarak gün aşırı 7 kez uygulandı. Ardı sıra 15-21. günlerde doğrudan
konjonktiva üzerine serum fizyolojik içinde %2'lik Ovalbumin 7 kez damlatıldı.
Ait olduğu gruba göre TK ilgili dozlarda i.p. olarak uygulandı. Konjonktiva
dokusu mast hücre sayıları (MHS) ile histopatolojik ve immünohistokimyasal MCT, TGFβ ve TNFα boyama sonuçları istatistiksel
olarak değerlendirildi.

Bulgular: Timokinonun tek başına sistemik uygulanması
konjonktiva histolojisinde değişikliğe neden olmadı. Ovalbüminle duyarlı hale
getirilen AK grubu kontrol grubuyla karşılaştırıldığında, konjonktiva
epitelindeki MHS istatistiksel olarak anlamlı artış gösterdi (p<0,001).
Deksametazon tedavi grubunda (p<0,001) olduğu gibi; TK tedavi
gruplarında da MHS, AK grubuna göre daha düşük bulundu ancak bu fark
istatistiksel olarak anlamlı değildi. TGF-β
ile negatif boyanma, TNF-α ile zayıf fokal boyanma tedavi gruplarının ortak
bulgusu olarak saptandı. 

Sonuç: Bu çalışmadaki doz ve sürelerle uygulanan ovalbümin,
deneysel çalışmalar için uygun bir AK modeli oluşturmaktadır. Timokinonun
uygulanan dozlarda yan etki oluşturmadığı ve AK gelişen durumlarda da kısmen
anti-inflamatuar yönü ile tedaviye destek olabileceği, ancak istenen
anti-alerjik etkiyi göstermediği düşünülmektedir.

Keywords

Alerjik konjuncktivit modeli, çörek otu, timokinon

References

• Leonardi A, DeFranchis G, Zancanaro F et al. Identification of local Th2 and Th0 lymphocytes in vernal conjunctivitis by cytokine flow cytometry. Invest Ophthalmol Vis Sci. 1999;40:3036-3040.
• Calder VL, Jolly G, Hingorani M et al. Cytokine production and mRNA expression by conjunctival T-cell lines in chronic allergic eye disease. Clin Exp Allergy. 1999;29:1214-1222. doi:10.1046/j.1365-2222.1999.00585.x
• Merdler I, Hassidim A, Sorkin N, Shapira S, Gronovich Y, Korach Z. Keratoconus and allergic diseases among Israeli adolescents between 2005 and 2013. Cornea. 2015;34:525-529. doi:10.1097/ICO.0000000000000416
• Nivenius E, Montan P. Spontaneous corneal perforation with atopic keratoconjunctivitis: a case series and literature review. Acta Opthalmol. 2015;93:383-387. doi: 10.1111/aos.12617
• Naderan M, Rajabi MT, Zarrinbakhsh P, Bakhshi A. Effect of allergic diseases on keratoconus severity. Ocul Immunol Inflamm. 2017;25:418-423. doi: 10.3109/09273948.2016.1145697
• Solomon A. Corneal complications of vernal keratoconjunctivitis. Curr Opin Allergy Clin Immunol. 2015;15:489-494. doi:10.1097/ACI.0000000000000202
• La Rosa M, Lionetti E, Reibaldi M et al. Allergic conjunctivitis: A comprehensive review of the literature. Ital J Pediatr. 2013;39:1-8. doi:10.1186/1824-7288-39-18.
• Shaker M, Salcone E. An update on ocular allergy. Curr Opin Allergy Clin Immunol. 2016;16:505-510. doi: 10.1097/ACI.0000000000000299
• Schneider-Stock R, Fakhoury IH, Zaki AM, El-Baba CO, Gali-Muhtasib HU. Thymoquinone: Fifty years of success in the battle against cancer models. Drug Discov Today. 2014;19:18-30. doi:10.1016/j.drudis.2013.08.021
• Woo CC, Kumar AP, Sethi G, Tan KH. Thymoquinone: Potential cure for inflammatory disorders and cancer. Biochem Pharmacol. 2012;83:443-451. doi: 10.1016/j.bcp.2011.09.029
• Wang W, Zheng M. Nuclear factor kappa B pathway down-regulates aquaporin 5 in the nasal mucosa of rats with allergic rhinitis. Eur Arch Otorhinolaryngol. 2011;268:73-81. doi: 10.1007/s00405-010-1282-3
• Xu YY, Liu X, Dai LB, Zhou SH. Effect of Tong Qiao drops on the expression of eotaxin, IL-13 in the nasal mucosa of rats with allergic rhinitis. J Chin Med Assoc. 2012;75:524-529. doi: 10.1016/j.jcma.2012.07.003
• Günel C, Demirci B, Eryılmaz A, Yılmaz M, Meteoğlu İ, Ömürlü İK, Başal Y. Inhibitory effect of Pycnogenol® on airway inflammation in ovalbumin-induced allergic rhinitis. Balkan medical journal, 2016; 33:620-626. doi: 10.5152/balkanmedj.2016.150057
• Unsal AIA, Basal Y, Birincioglu S, Kocaturk T, Cakmak H, Unsal A, Cakiroz G, Eliyatkın N, Yukselen O, Demirci B. Ophthalmic adverse effects of nasal decongestants on an experimental rat model. Arquivos brasileiros de oftalmologia. 2018;81:53-58.doi: 10.5935/0004-2749.20180012
• Abukhader MM. The effect of route of administration in thymoquinone toxicity in male and female rats. Indian J Pharm Sci. 2012;74:195-200. doi: 10.4103/0250-474X.106060
• Al-Ali A, Alkhawajah AA, Randhawa MA, Shaikh NA. Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats. J Ayub Med Coll Abbottabad. 2008;20:25-27.
• El Gazzar M, El Mezayen R, Nicolls MR, Marecki JC, Dreskin SC. Downregulation of leukotriene biosynthesis by thymoquinone attenuates airway inflammation in a mouse model of allergic asthma. Biochim Biophys Acta. 2006;1760:1088-1095. doi: 10.1016/j.bbagen.2006.03.006
• Mansour M, Tornhamre S. Inhibition of 5-lipoxygenase and leukotriene C4 synthase in human blood cells by thymoquinone. J Enzyme Inhib Med Chem. 2004;19:431-436. doi:10.1080/14756360400002072
• Radad K, Hassanein K, Al-Shraim M, Moldzio R, Rausch WD. Thymoquinone ameliorates lead-induced brain damage in Sprague Dawley rats. ExpToxicol Pathol.2014;66(1):13-17. doi:10.1016/j.etp.2013.07.002
• Ulu R, Dogukan A, Tuzcu M et al. Regulation of renal organic anion and cation transporters by thymoquinone in cisplatin induced kidney injury. Food Chem Toxicol. 2012;50:1675-1679. doi:10.1016/j.fct.2012.02.082
• Isik AF, Kati I, Bayram I, Ozbek H. A new agent for treatment of acute respiratory distress syndrome: Thymoquinone. An experimental study in a rat model. Eur J Cardiothorac Surg. 2005;28:301-305. doi:10.1016/j.ejcts.2005.04.012
• Tekeoglu I, Dogan A, Ediz L, Budancamanak M, Demirel A. Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat models. Phytother Res. 2007;21:895-897. doi:10.1002/ptr.2143