Early and late preventive effect of Nigella sativa on the bleomycin-induced pulmonary fibrosis in rats: An experimental study

Document Type: Original Research Article

Authors

1 Physiology Research Center of Kerman University of Medical Sciences, Kerman, Iran

2 Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

3 Department of Pharmacognosy, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

4 Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Science, Kerman, Iran

5 Department of Pharmacy, Kerman University of Medical Science, Kerman, Iran

6 Herbal & Traditional Medicines Research Center, Faculty of Pharmacy Kerman University of Medical Sciences, Kerman, Iran

7 Neurogenic Inflammation Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

8 Assistant Professor of Plant Protection, Departement of agriculture

Abstract

Objective: Pulmonary fibhrosis is a disease of the connective tissues in the respiratory system. Nigella sativa has been used for the treatment of pulmonary diseases like asthma. This study investigated the early and late preventive effect of methanolic extract of N. sativa on a bleomycin- induced pulmonary fibrosis model.
Materials and Methods: This study was carried out using 52 rats. Pulmonary fibrosis was induced by a single endotracheal injection of bleomycin (5 mg/kg). Extract of N. sativa (500 mg/kg per day) or methylprednisolone succinate (4 mg/kg per day) was injected intraperitoneally in two periods (i.e. days 1-14 as early preventive group and days 15-28 days as late preventive group). The lung tissues were histologically examined at the end of each period and inspected for the amount of hydroxyproline and biomarkers of oxidative stress.
Results: The pulmonary inflammation and fibrosis were significantly decreased in groups treated with methylprednisolone and N. sativa extract compared to bleomycin group in both early and late prevention groups (p<0.001). The hydroxyproline concentration in pulmonary tissue was significantly decreased in N. sativa and methylprednisolone groups compared to the bleomycin group in both prevention groups (p<0.001). Significant reductions in lipid peroxidation (p<0.001) and increases in catalase activity were also observed in N. sativa and methylprednisolone groups compared to bleomycin group.
Conclusion: This study suggested that N. Sativa extract is effective for early and late prevention of pulmonary fibrosis and inflammation. However, more studies are needed to identify its anti-inflammatory and anti-fibrotic mechanisms in the respiratory system.

Keywords

Main Subjects


Al-Ameen NM, Altubaigy F, Jahangir T, Mahday IA, Esmaeel Abdurrahman Mohammed EA and Musa OAA. 2011. Effect of Nigella sativa and bee honey on pulmonary, hepatic and renal function in Sudanese in Khartoum state. J Med Plant Res, 5: 6857-6863.

Antoniou KM, Pataka A, Bouros D, Siafakas NM. 2007. Pathogenetic pathways and novel pharmacotherapeutic targets in idiopathic pulmonary fibrosis. Pulm Pharmacol Ther, 20: 453-461.

Aoki F, Kurabayashi M, Hasegawa Y, Kojima I. 2005. Attenuation of bleomycin-induced pulmonary fibrosis by follistatin. Am J Respir Crit Care Med, 172: 713-720.

Ashcroft T, Simpson JM, Timbrell V. 1988. Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol, 41: 467-470.

Ashraf SS, Rao MV, Kaneez FS, Qadri S, Al-Marzouqi AH, Chandranath IS, Adem A. 2011. Nigella sativa extract as a potent antioxidant for petrochemical-induced oxidative stress. J Chromatogr Sci, 49: 321-326.

Azambuja E, Fleck JF, Batista RG, Menna Barreto SS. 2005. Bleomycin lung toxicity: who are the patients with increased risk? Pulm Pharmacol Ther, 18: 363-366.

Aziz Dollah M, Parhizkar S, Izwan M. 2013. Effect of Nigella sativa on the kidney function in rats. Avicenna J Phytomed, 3: 152-158.

Badary OA, Taha RA, Gamal el-Din AM, Abdel-Wahab MH. 2003. Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol, 26: 87-98.

Beers RF, Jr., Sizer IW. 1952. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem, 195: 133-140.

Boskabady MH, Javan H, Sajady M, Rakhshandeh H. 2007. The possible prophylactic effect of Nigella sativa seed extract in asthmatic patients. Fundam Clin Pharmacol, 21: 559-566.

Boskabady MH, Keyhanmanesh R, Khameneh S, Doostdar Y, Khakzad MR. 2011a. Potential immunomodulation effect of the extract of Nigella sativa on ovalbumin sensitized guinea pigs. ‎J Zhejiang Univ Sci B, 12: 201-209.

Boskabady MH, Keyhanmanesh R, Khamneh S, Ebrahimi MA. 2011b. The effect of Nigella sativa extract on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea pigs. Clinics (Sao Paulo, Brazil), 66: 879-887.

Boskabady MH, Mohsenpoor N, Takaloo L. 2010. Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomedicine, 17: 707-713.

Bringardner BD, Baran CP, Eubank TD, Marsh CB. 2008. The role of inflammation in the pathogenesis of idiopathic pulmonary fibrosis. Antioxid Redox Signal, 10: 287-301.

Cantin AM, Hubbard RC, Crystal RG. 1989. Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis. Am Rev Respir Dis, 139: 370-372.

Cantin AM, North SL, Fells GA, Hubbard RC, Crystal RG. 1987. Oxidant-mediated epithelial cell injury in idiopathic pulmonary fibrosis. Clin Investig, 79: 1665-1673.

Ceretta LB, Reus GZ, Abelaira HM, Ribeiro KF, Zappellini G, Felisbino FF, Steckert AV, Dal-Pizzol F, Quevedo J. 2012. Increased oxidative stress and imbalance in antioxidant enzymes in the brains of alloxan-induced diabetic rats. Exp Diabetes Res, 2012: 302682.

Chen F, Gong L, Zhang L, Wang H, Qi X, Wu X, Xiao Y, Cai Y, Liu L, Li X, Ren J. 2006. Short courses of low dose dexamethasone delay bleomycin-induced lung fibrosis in rats. Eur J Pharmacol, 536: 287-295.

Chen M, CheungFW, Hung Chan M, Kwan Hui P, Ip S-P, Hin Ling Y, Che C-T, Keung Liu W. 2012. Protective roles of Cordyceps on lung fibrosis in cellular and rat models. J Ethnopharmacol, 143: 448–454.

Crouch E. 1990. Pathobiology of pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol, 259: L159-L184.

Crystal RG, Bitterman PB, Rennard SI, Hance AJ, Keogh BA. 1984. Interstitial lung diseases of unknown cause. Disorders characterized by chronic inflammation of the lower respiratory tract (first of two parts). N Engl J Med, 310: 154-166.

Danladi J, Abdulsalam A, Timbuak J, Ahmed S, Dahiru A. 2013. Hepatoprotective Effect of Black Seed (Nigella sativa) oil on Carbon Tetrachloride (CCl4) Induced Liver Toxicity in Adult Wistar Rats. 4: 56-62.

Demedts M, Costabel U. 2002. ATS/ERS international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Eur Respir J, 19: 794-796.

Dollah MA, Parhizkar S, Latiff LA, Hassan MHB. 2013. Toxicity Effect of Nigella Sativa on the Liver Function of Rats. Adv Pharm Bull, 3: 97-102.

Esterbauer H, Cheeseman KH. 1990. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. ‎Methods Enzymol, 186: 407-421.

Gali-Muhtasib H, El-Najjar N, Schneider-Stock R. 2006. The medicinal potential of black seed (Nigella sativa) and its components. Phytomedicine, 2: 133-153.

Gao J, Huang Y, Li P, Xu D, Li J, Liu Y, Huang Z, Wu Q, Shao X. 2011. Antifibrosis effects of total glucosides of Danggui–Buxue–Tang in a rat model of bleomycin-induced pulmonary fibrosis. J Ethnopharmacol, 136: 21-26.

Garantziotis S, Steele MP, Schwartz DA. 2004. Pulmonary fibrosis: thinking outside of the lung. J Clin Invest, 114: 319-321.

Ghannadi A, Hajhashemi V, Jafarabadi H. 2005. An investigation of the analgesic and anti-inflammatory effects of Nigella sativa seed polyphenols. J Med Food, 8: 488-493. 

Ghosheh OA, Houdi AA, Crooks PA. 1999. High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). J Pharm Biomed Anal, 19:757-762.

Homer RJ, Elias JA, Lee CG, Herzog E. 2011. Modern concepts on the role of inflammation in pulmonary fibrosis. Arch Pathol Lab Med, 135: 780-788.

Hossein BM, Nasim V, Sediqa A. 2008. The protective effect of Nigella sativa on lung injury of sulfur mustard-exposed Guinea pigs. Exp Lung Res, 34: 183-194.

Keyhanmanesh R, Bagban H, Nazemiyeh H, MirzaeiBavil F, Alipour MR, Ahmady M. 2013. The Relaxant Effects of Different Methanolic Fractions of Nigella sativa on Guinea Pig Tracheal Chains. Iran J Basic Med Sci, 16: 123-128.

Keyhanmanesh R, Gholamnezhad Z, Boskabady MH. 2014a. The relaxant effect of Nigella sativa on smooth muscles, its possible mechanisms and clinical applications. Iran J Basic Med Sci, 17: 939-949.

Keyhanmanesh R, Nazemiyeh H, Mazouchian H, Bagheri Asl MM, Karimi Shoar M, Alipour MR, Boskabady MH. 2014b. ,Exposed to Cigarette Smoke Modulates In Vitro Tracheal Responsiveness. Iran Red Crescent Med J, 16: e10421.

Kim DS, Collard HR, King TE, Jr. 2006. Classification and natural history of the ,Thorac Soc, 3: 285-292.

Kinnula VL, Fattman CL, Tan RJ, Oury TD. 2005. Oxidative stress in pulmonary fibrosis: a possible role for redox modulatory therapy. Am J RespirCrit Care Med, 172: 417-422.

Knight JA. 1998. Free radicals: their history and current status in aging and disease. ‎Ann Clin Lab Sci, 28: 331-346.

Kuwano K, Kunitake R, Maeyama T, Hagimoto N, Kawasaki M, Matsuba T, Yoshimi M, Inoshima I, Yoshida K, Hara N. 2001. Attenuation of bleomycin-induced pneumopathy in mice bya caspase inhibitor. Am J Physiol Lung Cell Mol Physiol, 280: L316-325.

Lam RY, Woo AY, Leung PS, Cheng CH. 2007. Antioxidant actions of phenolic compounds found in dietary plants on low-density lipoprotein and erythrocytes in vitro. J Am CollNutr, 26: 233-242.

Leong XF, Rais Mustafa M, Jaarin K. 2013. Nigella sativa and Its Protective Role in Oxidative Stress and Hypertension. J Evid Based Complementary Altern Med, 2013:120732.

Liang X, Tian Q, Wei Z, Liu Fe, Chen J, Zhao Y, Qu P, Huang X, Zhou X, Liu N. 2011. Effect of Feining on bleomycin-induced pulmonary injuries in rats. J Ethnopharmacol, 134: 971-976.

Mandegary A, Sezavar M, Saeedi A, Amirheidari B, Naghibi B. 2012. Oxidative stress induced in the workers of natural gas refineries, no role for GSTM1 and GSTT1 polymorphisms. Hum ExpToxicol, 31: 1271-1279.

Meziti A, Meziti H, Boudiaf K, Mustapha B, Bouriche H. 2012. Polyphenolic profile and antioxidant activities of Nigella sativa seed extracts in vitro and in vivo. World Acad Sci Eng Technol, 64: 24–32.

Moeller A, Rodriguez-Lecompte JC, Wang L, Gauldie J, Kolb M. 2006. Models of pulmonary fibrosis. Drug Discov Today Dis Models, 3: 243-249.

Onoshe S, Madusolumuo MA. 2014. Effect of Hexane Seed Extract of Nigella Sativa on Cadmium Induced Renal Dysfunction in Rats. Am J Res Commun, 2: 158-171.

Pejman L, Omrani H, Mirzamohammadi Z, Keyhanmanesh R. 2014. Thymoquinone, the main constituent of Nigella sativa, affects adenosine receptors in asthmatic guinea pigs. Iran J Basic Med Sci, 17: 1012-1019.

Pincemail J. 1995. Free radicals and antioxidants in human diseases Analysis of free radicals in biological systems. Springer, p 83-98

Reddy GK, Enwemeka CS. 1996. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem, 29: 225-229.

Saad SI. 1975. Clasification of flower plants.2nded. Alexandria: The general Egyptian Book Co,pp 412-413.

Samareh Fekri M, Poursalehi HR, Najafipour H, Dabiri S. 2013. Pulmonary complications of gastric fluid and bile salts aspiration, an experimental study in rat. Iran J Basic Med Sci, 16: 790-796.

Samareh Fekri M, Poursalehi HR, Sharifi Far F,  Mandegari A and et al.2015. The Effect of Methanol Extract of Fennel on Bleomycin – Induced Pulmonary Fibrosis in Rats. J  Kmu Med Sci, 22: 470-483. 

Sies H. 1985. Oxidative stress: introductory remarks. Academic Press, 1985. pp. 1–8.

Spatz L, Bloom AD. 1992. Biological consequences of oxidative stress: Implicationsfor cardiovascular disease and carcinogenesis. Oxford University Press, 138-161.

Sur S, Wild JS, Choudhury BK, Sur N, Alam R, Klinman DM. 1999. Long term prevention of allergic lung inflammation in a mouse model of asthma by CpGoligodeoxynucleotides. J Immunol, 162: 6284-6293.

Thannickal VJ, Flaherty KR, Martinez FJ, Lynch 3rd JP. 2004. Idiopathic pulmonary fibrosis: emerging concepts on pharmacotherapy. Expert Opin Pharmacother, 5: 1671-1686.

Tzurel A, Segel MJ, Or R, Goldstein RH, Breuer R. 2002. Halofuginone does not reduce fibrosis in bleomycin-induced lung injury. Life sciences, 71: 1599-1606.

Venkatesan N, Punithavathi V, Chandrakasan G. 1997. Curcumin protects bleomycin-induced lung injury in rats. Life Sci, 61: Pl51-58.

Walters DM, Cho HY, Kleeberger SR. 2008. Oxidative stress and antioxidants in the pathogenesis of pulmonary fibrosis: a potential role for Nrf2. Antioxid Redox Signal, 10: 321-332.

Wang Q, Giri SN, Hyde DM, Li C. 1991. Amelioration of bleomycin-induced pulmonary fibrosis in hamsters by combined treatment with taurine and niacin. Biochem Pharmacol, 42: 1115-1122.

Woessner Jr J. 1961. The determination of hydroxyproline in tissue and protein samples containing small proportions of this iminoacid. Arch Biochem Biophys, 93: 440-447.

Zaher KS, Ahmad W, Zerizer SN. 2008. Observations on the biological effects of black cumin seeds (Nigella sativa) and green tea (Camellia sinensis). Glob Vet, 2: 198-204.

Zhou XM, Zhang GC, Li JX, Hou J. 2007. Inhibitory effects of Hu-qi-yin on the bleomycin-induced pulmonary fibrosis in rats. J Ethnopharmacol, 111: 255-264.