Supplementation of Thymoquinone and Carob Together in the Experimental Rat Asthma Model: Oxidative Effect on the Liver Tissue

Year 2022, Volume: 9 Issue: 2, 65 - 72, 30.06.2022

Özge Akyazı , Şule Coşkun Cevher

https://doi.org/10.17350/HJSE19030000256

Abstract

Asthma, an important public health problem, is a common, potentially serious, medical condition in children, adults and pregnant women. The aim of this study is to investigate the effects of the combined use of thymoquinone and carob on liver tissue oxidative events, following the experimental asthma model. 18 male albino wistar rats were divided into 3 groups as: the control group, the experimental asthma group and treated group (A+TQ+C). In the asthmatic groups, ovalbumin and alum were given intraperitoneally on the 0 and 14th days, and sensitized by inhalation on the 21st, 22nd and 23rd days. In the next 5 days, thymoquinone and carob were given to the group to be treated by intragastric gavage method. In all experimental groups, glutathione (GSH), ascorbic acid (AA), malondialdehyde (MDA) and nitric oxide (NOx) levels were measured spectrophotometrically to evaluate the oxidant-antioxidant status in the liver tissue of rats. While liver tissue GSH and AA levels increased, NOx levels were found to decrease following thymoquinone and carob administration in the treated group (A+TQ+C) when compared other groups (Control and Asthma). However, MDA levels, which are the indicator of lipid peroxidation, were found to be statistically significantly increased in the treated group (A+TQ+C) (p<0.05) when compared the other groups (Control and Asthma). As a result, the co-administration of thymoquinone and carob has a regulatory effect that eliminates the possible oxidative effects of asthma, giving hope that it may be a new treatment for children, adults and pregnant women.

Keywords

Asthma, Thymoquinone, Carob, Liver, Oxidative stress

Supporting Institution

BAP

Project Number

05/2016-22

References

• [1] (GINA) GI for A. Global Strategy for Asthma Management and Prevention (2018).
• [2] Busse WW. Expert panel report 3 (EPR-3): guidelines for the diagnosis and management of asthma- summary report 2007,National Asthma Education and Prevention Program. Journal Allergy Clinical Immunology 120(5) (2007) 94–138.
• [3] Kılınç O, Akgün M. Astım Tanı ve Tedavi Rehberi 2016. Türk Toraks Derneği Dergisi 17 (2016) 1-4.
• [4] Cukic V, Lovre V, Dragisic D, Ustamujic A. Asthma and Chronic Obstructive Pulmonary Disease (COPD) – Differences and Similarities. Mater Sociomed 24(2) (2012) 100–105.
• [5] Beasley R, Roche WR, Roberts JA, Holgate ST. Cellular events in the bronchi in mild asthma and after bronchial provocation. American Review of Respiratory Disease 139 (1989) 806.
• [6] Elias JA, Lee CG, Zheng T, Ma B, Homer RJ, Zhu Z. New insights into the pathogenesis of asthma. The Journal of Clinical Investigation 111 (2003)291- 297.
• [7] Salomonsson M, Malinovschi A, Kalm-Stephens P, Dahlin JS, Janson C, Alving K, Hallgren J. Circulating mast cell progenitors correlate with reduced lung function in allergic asthma. Clinical Experimental Allergy Abstract,2019.
• [8] Kokuludag A. Monoclonal anti-IgE antibody treatment for asthma. Türkiye Klinikleri J Allergy-Asthma 3 (2001 )27-33.
• [9] Köksal B. Astımlı Cocuklarda Serum Angiopoietin-1, Angiopoietin-2, Vascular Endothelial Growth Faktör Tümör Necrosis Faktör-α Düzeylerinin Değerlendirilmesi, Yan Dal Uzmanlık Tezi, Başkent Üniversitesi Sağlık Bilimleri Enstitüsü, Ankara, pp. 1-9,2012.
• [10] Feltıs BN, Wıgnarajah D, Reıd DW, Ward C, Hardıng R, Walters EH. Effects of inhaled fluticasone on angiogenesis and vascular endothelial growth factor in asthma. Thorax 62(4) (2007) 314-319.
• [11] Kaltalıoğlu K. Trombosit kökenli büyüme faktörü’nün yara dokusu oksidatif olayları üzerine etkileri, Yüksek Lisans Tezi, Gazi Üniversitesi Fen Bilimleri Enstitüsü, Ankara, pp. 32-41,2012.
• [12] Sen CK. Oxidants and antioxidants in exercise. Journal of applied physiology 79(3) (1995) 675-86.
• [13] Salem ML. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. International Immunopharmachology 5 (2005) 1749-70.
• [14] Casas-Grajales S, Muriel P. Antioxidants in liver health. World J Gastrointest Pharmacol Ther 6 (3) (2015) 59–72.
• [15] Anapalı M, Balkan E. Karaciğer Fibrozisinde Sitokinlerin Rolü. Kafkas Med Sci 11 (1) (2021) 111–122.
• [16] Aydilek N, Aksaksal M. Testosteronun Tavşanlarda Karaciğer Antioksidan Sistemi Üzerine Etkisi. YYÜ Vet Fak Derg 14 (2) (2003) 22-25.
• [17] Fitzpatrick AM, Jones DP, Brown LAS. Glutathione Redox Control of Asthma: From Molecular Mechanisms to Therapeutic Opportunities. Antioxid Redox Signal 17(2) (2012) 375–408.
• [18] Temiz Ö. Oreochromis niloticus'un Karaciğerinde Fungisit Propiconazole'un Oksidatif Stres Parametreleri ve Antioksidan Sistem Enzimleri Üzerine Etkileri. J Anatolian Env and Anim Sciences 4(1) (2019) 43-47.
• [19] Türktaş H, Şekerel B, Karakaya G, Yıldız F, Yorgancıoğlu A. Astım tedavisinde uzun etkili beta-2 agonistlerin yeri ve güvenilirliği. Tüberküloz ve Toraks Dergisi 59(4) (2011) 409-415.
• [20] Erge D. Metakolinle Atak Geliştiren Kronik Astımlı BALB/C Farelerde Nebulize Sildenafilin Akciğer Histolojisi, Oksijen Saturasyonu ve Kan Gazi Parametreleri Üzerine Etkileri, Yan Dal Uzmanlık Tezi, Dokuz Eylül Üniversitesi Sağlık Bilimleri Enstitüsü, İzmir,2010.
• [21] Bahmania M, Zargaranb A, Rafieian-Kopaei M. Identification of medicinal plants of Urmia for treatment of gastrointestinal disorders. Revista Brasileria Farmacognosia 24 (2014) 468-480.
• [22] El Gazzar M, El Mezayen R, Mareckı JC, Nıcolls MR, Canastar A, Dreskın S.C. Anti-inflammatory effect of thymoquinone in a mouse model of allergic lung inflammation. International Immunopharmacology 6 (2006) 1135-1142.
• [23] Klenow SM, Glei R, Owen and B. Pool-Zobel. Carob Fibre compounds modulate parameters of cell growth differently in human HT29 colon adenocarcinoma cell than in LT97colon adenoma cell. Food and Chemical Toxicology 46(4) (2008) 1389-1397.
• [24] Mansour M, Tornhamre S. Inhibition of 5-lipoxygenase and leukotriene C4 synthase in human blood cells by thymoquinone. Journal of Enzyme Inhibition and Medicinal Chemistry 19 (2004) 431-6.
• [25] Halliwell B, Gutteridge JMC. Oxygen toxicity, oxygen radicals, transition metals and disease. Biochemical Journal 219 (1984) 1-14.
• [26] Farooqui Z, Shahid F, Khan AA, Khan F. Oral administration of Nigella sativa oil and thymoquinone attenuates long term cisplatin treatment induced toxicity and oxidative damage in rat kidney. Biomed Pharmacother 96 (2017) 912-23.
• [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. Biochimica et Biophysica Acta 1760(7) (2006) 1088-95.
• [28] Kumazama S, Taniguchi M, Suzuki Y, Shimura M, Kwon MS, Nakayama T. Antioxidant activity of polyphenols in carob pods. Journal of agricultural and food chemistry 50 (2002) 373–377.
• [29] Makris DP, Kefalos P. Carob pods (Ceratonia silique L.) as a source of polyphenolic antioxidants. Food Technology Biotechnology 42 (2004) 105–108.
• [30] Moh'D Khaiv J, EL-shatnawi and Khalil I E. Chemical Composition And Livestock Ingestion of carob (Ceratonia siliqua L.) seeds. Journal of Range Management 54(6) (2001) 669-673.
• [31] Karabulut A, Canbolat O, Kamalak A. Evaluation of carob, Ceratonia siliqua Pods as a feed for sheep, Livestock Research for Rural Development, Kahramanmaraş, Turkey, 18(17),2006.
• [32] Avallone R, Olessi M, Baraldi M, Monzani A. Determination of chemical composition of carob (Ceratonia siliqua): Protein, Fat, Carbohydrates, and Tannins. Journal of food composition and Analysis 10(2) (1997) 166- 172.
• [33] Mokhtari M, Sharifi E, Azadian Sh. The effects of hydro alcoholic extract of Ceratonia siliqua L. seeds on pituitary – testis hormones and spermatogenesis in rat. Advances in Environmental Biology 6(10) (2012) 2778- 2783.
• [34] Krokou A, Stylianou M, Agapiou A. Assessing the volatile profile of carob tree (Ceratonia siliqua L.). Environmental science and pollution research international Abstract,2019.
• [35] Farag MA, El-Kersh DM, Ehrlich A, Choucry MA, El-Seedi H, Frolov A, Wessjohann LA. Variation in Ceratonia siliqua pod metabolome in context of its different geographical origin, ripening stage and roasting process. Food Chemistry 283 (2019) 675-687.
• [36] Christou C, Poulli E, Yiannopoulos S, Agapiou A. GC-MS analysis of D-pinitol in carob: Syrup and fruit (flesh and seed). Journal of chromatography B Analytical technologies in the biomedical and life sciences 1116 (2019) 60-64.
• [37] Papaefstathiou E, Agapiou A, Giannopoulos S, Kokkinofta R. Nutritional characterization of carobs and traditional carob products. Food Science Nutrition 6(8) (2018) 2151-2161.
• [38] Fadhil Ahmed A, Coskun Cevher S. The Preventive Effect of Thymoquinone and Ceratonia Siliqua L. in Experimental Asthmatic Pregnant Rats: Histologically and Immunohistochemically Evaluation. Hittite Journal of Science and Engineering 6(3) (2019) 215-222.
• [39] Moura CTM, Bezerra FC, Moraes IM, Magalhaes PJC, Capaz FR. Increase responsiveness to 5- hydroxytryptamine after antigenic challenge is inhibited by nifedipine and nif lumic acid in rat trachea in vitro. Clin Exp Pharmacol Physiol 32 (2005) 1119–1123.
• [40] Yang EJ, Lee JS, Song BB, Yun CY, Kim DH, Kim IS. Anti-ınflammatory effects of ethanolic extract from Lagerstroemia indica on airway inflammation in mice. J Ethnopharmacol 136 (2011) 422–427.
• [41] Buege JA, Aust SD. Microsomal Lipid Peroxidation. Methods in Enzymology 52 (1978) 302-310.
• [42] Ellman GL. Tissue sulfhydryl groups. Archives of biochemistry and biophysics 82(1) (1959) 70-7.
• [43] Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5(1) (2001) 62-71.
• [44] Boskabady MH, Sheiravi N. Inhibitory effect of Nigella sativa on histamine receptors of isolated guinea pig tracheal chains. Pharmaceutical Biology 40(8) (2002) 596-602.
• [45] Ayaz FA, Torun H, Ayaz S, Correia PJ, Alaiz M, Sanz C, Gruz J, Strand M. Determination of chemical composition of Anatolian carob pod (Ceratonia siliqua L.), Sugars, amino and organic acids, minerals and phenolic compounds. Journal of Food Quality 30 (2007) 1040-1055.
• [46] Tokeshi I, Yoshimoto T, Muto N, Nakamura S, Ashizawa K, Nakada T, Tatemoto H. Antihyaluronidase action of ellagic acid effectively prevents polyspermy as a result of suppression of the acrosome reaction induced by spermzona interaction during in vitro fertilization of porcine oocytes. The Journal of Reprodaction and Development 53(4) (2007) 755-764.
• [47] Chekchaki N, Khaldi T, Rouibah Z, Rouag M, Sekiou O, Messarah M, Boumendjel A. Anti-inflammatory and antioxidant effects of two extracts from Pistacia lentiscus in liver and erythrocytes, in an experimental model of asthma. International Journal of Pharmaceutical Sciences Review and Reserch 42(1) (2017) 77– 84.
• [48] Oskouei Z, Akaberi M, Hosseinzadeh H. A glance at black cumin (Nigella sativa) and its active constituent, thymoquinone, in ischemia: a review. Iranian journal of basic medical sciences 21(12) (2018) 1200- 1209.
• [49] Houghton PJ, Zarka R, Heras BDL, Hoult JR. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Medicine 61 (1995) 33-36.
• [50] El-Abhar HS, Abdallah DM, Saleh S. Gastroprotective activity of N.sativa oil and its constituent, TQ, against gastric mucosal injury induced by ischaemia/reperfusion in rats. Journal of Ethnopharmacology 83 (2003) 251-258.
• [51] Ayan NN. Streptozotosin ile Diyabet Oluşturulan Rat Karaciğer Dokusunda Oksidatif Stres, Paraoksonaz-1 Aktivitesi Ve Stobadin’in Koruyucu Etkisinin Araştırılması, Uzmanlık Tezi, Gazi Üniversitesi Sağlık Bilimleri Enstitüsü, Ankara,2007.
• [52] Lu SC. Regulation of hepatic glutathione synthesis: current concepts and controversies. Faseb Journal 13 (1999) 1169-1183.
• [53] Almohawes ZN, Alruhaimi HS. Effect of Lavandula dentata extract on Ovalbumin-induced Asthma in Male Guinea Pigs. Brazilian journal of biology 80 (6) (2019) 1-10.
• [54] Laxmi V, Gupta R, Bhattacharya SK, Ray A, Gulati K. Inhibitory effects of sildenafil and tadalafil on inflammation, oxidative stress and nitrosative stress in animal model of bronchial asthma. Pharmacological reports 71(3) (2019) 517521.
• [55] Mates JM. Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology. Toxicology 153 (2000) 83–104.
• [56] Shigeki Enomoto S, Asano R, Iwahorı Y, Naruı T, Okada Y, Sıngab ANB, Okuyama T. Hematological Studies On Black Cumin Oil From The Seeds Of Nigella Sativa L. Biological and Pharmaceutical Bulletin 24(3) (2001) 307-310.
• [57] Burits M, Bucar F. Antioxidant activity of Nigella sativa essential oil. Phytotherapy Research 14(5) (2000) 323-328.
• [58] Mao Y, Zhan Y, Huang Y. Vitamin D and asthma: A Mendelian randomization study. Annals Allergy Asthma Immunology 119(1)(2017) 95-97.
• [59] Nasser MZ, Ezzat DA. Association of -308G/A Polymorphism and Serum Level of TNF- α with Bronchial asthma in Children. The Egyptian journal of immunology 25(2) (2018) 117-124.
• [60] Mekhoukhe A, Kicher H, Ladjouzi A, Medouni-Haroune L, Brahmi F, Medouni-Adrar S, Madani K. Antioxidant activity of carob seeds and chemical composition of their bean gum by products. Journal of complementary & integrative medicine 16(1) (2018).
• [61] Zhang Y, Zhang L, Wang S, Haoshen H, Wei E. Montelukast modulates lung cysLT 1 receptor expression and eosinophillic inflammation in asthmatic mice. Acta Pharmacol Sinica 25(10)(2004) 1341-1346.
• [62] Şahin NÖ. Thymoquınon’un Deneysel Astım Modelinde Antiastmatik Etkisinin Araştırılması, Yüksek Lisans Tezi, Zonguldak Karaelmas Üniversitesi Sağlık Bilimleri Enstitüsü, Zonguldak, 2006.
• [63] Işık AF, Kati İ, Bayram İ, Özbek H. A new agent for treatment of acute respiratory distress syndrome: thymoquinone. An experimental study in a rat model. European Journal of Cardio Thoracic Surgery 20 (2005) 1- 5.
• [64] El-Dakhakhny M, Madi NJ, Lembert N, Ammon HP. Nigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygnase pro-ducts in polymorphonuclear leukocytes from rats. Journal Ethnopharmacol 81 (2002) 161-4.
• [65] Pazır F, Yüksel A. Keçiboynuzu Meyvesi (Ceratonia siliqua L.) ve Sağlık. Akademik Gıda 14(3) (2016) 302-306.
• [66] Mahgoub AA. TQ protects against experimental colitis in rats. Toxicology Letters 143 (2003) 133-143.