Protective and therapeutic effects of ethanolic extract of Nasturtium officinale (watercress) and vitamin E against bleomycin-induced pulmonary fibrosis in rats

Sanaz Ramezani , Iraj Javadi, Esmaeel Panahi Kokhdan, Navid Omidifar, Jafar Nikbakht, Heibatollah Sadeghi, Amir Hossein Doustimotlagh, Nazanin Danaei, Reza Abbasi, Hossein Sadeghi

Abstract


Background and purpose: Pulmonary fibrosis is a chronic disease of the lungs caused by inflammation, species of reactive oxygen, and immune defects. Antioxidant properties of Nasturtium officinale has been reported in some studies. Therefore, the objective of the current study was to evaluate the effect of ethanolic extract of Nasturtium officinale (EENO) on bleomycin (BLM)-induced lung fibrosis in rats.

Experimental approach: Forty adult male Wistar rats (180-220 g) were randomly divided into 5 experimental groups. Normal control, BLM control received a single dose of BLM (6 IU/kg) intratracheally only on the first day, EENO + BLM group received EENO (500 mg/kg) one week before intratracheal BLM instillation and two weeks afterward, BLM + EENO group and BML + vitamin E group received EENO (500 mg/kg) and vitamin E (500 mg/kg) half-hour after BLM installation, respectively. The animals were sacrificed on day 22. Change in body weight, lung index, serum level of malondialdehyde (MDA) and nitric oxide (NO) metabolite, lung tissue hydroxyproline content and lung pathology were assessed.

Findings/Results: Pre- or post-treatment with EENO attenuated pulmonary fibrosis as evidenced by normalized lung index, improved histological changes and inhibited collagen deposition (hydroxyproline) in the animal lung. EENO also decreased MDA and NO metabolite release in comparison to the BLM control. vitamin E (500 mg/ kg) also significantly inhibited the BLM-induced lung toxicity.

Conclusions and implications: EENO can prevent BLM-induced lung fibrosis in rats via antioxidant activities. However, more studies are needed to elicit the exact mechanism of this effect.

 

 


Keywords


Bleomycin; Fibrosis; Nasturtium officinale; Vitamin E.

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References


Hsu HS, Liu CC, Lin JH, Hsu TW, Hsu JW, Su K, et al. Involvement of ER stress, PI3K/AKT activation, and lung fibroblast proliferation in bleomycin-induced pulmonary fibrosis. Sci Rep. 2017;7:14272,1-11.

DOI:10.1038/s41598-017-14612-5.

Bik L, Sangers T, Greveling K, Prens E, Haedersdal M, van Doorn M. Efficacy and tolerability of intralesional bleomycin in dermatology: a systematic review. J Am Acad Dermatol. 2020;83(3):888-903.

DOI: 10.1016/j.jaad.2020.02.018.

Zuo WL, Zhao JM, Huang JX, Zhou W, Lei ZH, Huang YM, et al. Effect of bosentan is correlated with MMP‑9/TIMP‑1 ratio in bleomycin‑induced pulmonary fibrosis. Biomed Rep. 2017;6(2):201-205.

DOI: 10.3892/br.2016.832.

Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci. 2003;100(14):8407-8411.

DOI: 10.1073/pnas.1432929100.

Ma WH, Li M, Ma HF, Li W, Liu L, Yin Y, et al. Protective effects of GHK-Cu in bleomycin-induced pulmonary fibrosis via anti-oxidative stress and anti-inflammation pathways. Life Sci. 2020;241:117139.

DOI: 10.1016/j.lfs.2019.117139,1-13.

Wuyts WA, Agostini C, Antoniou KM, Bouros D, Chambers RC, Cottin V, et al. The pathogenesis of pulmonary fibrosis: a moving target. Eur Respir J. 2013;41(5):1207-1218.

DOI: 10.1183/09031936.00073012.

Abidi A, Kourda N, Feki M, Ben Khamsa S. Protective effect of Tunisian flaxseed oil against bleomycin-induced pulmonary fibrosis in rats. Nutr Cancer. 2020;72(2):226-238.

DOI: 10.1080/01635581.2019.1622741.

Khalvati B, Sheikhsaran F, Sharifzadeh S, Kalantari T, Behzad Behbahani A, Jamshidzadeh A, et al. Delivery of plasmid encoding interleukin-12 gene into hepatocytes by conjugated polyethylenimine-based nanoparticles. Artificial Cells, Nanomed. Biotechnol. 2017;45(5):1036-1344.

DOI: 10.1080/21691401.2016.1202256.

Dehshahri A, Sadeghpour H, Keykhaee M, Khalvati B, Sheikhsaran F. Enhanced delivery of plasmid encoding interleukin-12 gene by diethylene triamine penta-acetic acid (DTPA)-conjugated PEI nanoparticles. Appl Biochem Biotechnol. 2016;179(2):251-269.

DOI: 10.1007/s12010-016-1991-1.

Jo HE, Randhawa S, Corte TJ, Moodley Y. Idiopathic pulmonary fibrosis and the elderly: diagnosis and management considerations. Drugs Aging. 2016;33(5):321-334.

DOI: 10.1007/s40266-016-0366-1.

Yazdanparast R, Bahramikia S, Ardestani A. Nasturtium officinale reduces oxidative stress and enhances antioxidant capacity in hypercholesterolaemic rats. Chem Biol Interact. 2008;172(3):176-184.

DOI: 10.1016/j.cbi.2008.01.006.

Amiri H. Volatile constituents and antioxidant activity of flowers, stems and leaves of Nasturtium officinale R. Br. Nat Prod Res. 2012;26(2):109-115.

DOI: 10.1080/14786419.2010.534998.

Mazandarani M, Momeji A, Zarghami MP. Evaluation of phytochemical and antioxidant activities from different parts of Nasturtium officinale R. Br. in Mazandaran. Iran J Plant Physiol. 2012;3(2):659-664.

DOI: 10.22034/IJPP.2013.540676.

Simmonds MSJ, Howes MJR. Plants used in the treatment of diabetes. In: Soumyanath A, editor. Traditional medicine for modern times-antidiabetic plants. 1st ed. CRC Press; 2006. pp. 19-82.

Sadeghi H, Azarmehr N, Razmkhah F, Sadeghi H, Danaei N, Omidifar N, et al. The hydroalcoholic extract of watercress attenuates protein oxidation, oxidative stress, and liver damage after bile duct ligation in rats. J Cell Biochem. 2019;120(9):14875-14884.

DOI: 10.1002/jcb.28749.

Karami M, Mostafazadeh M, Sadeghi H, Sadeghi H, Mehraban F, Kokhdan EP, et al. Nephroprotective effect of Nasturtium officinale (watercress) ethanol extract and Vitamin E on vancomycin-induced nephrotoxicity in rats. Jundishapur J Nat Pharm Prod. 2018;13(1):e67178,1-8.

DOI: 10.5812/jjnpp.67178.

Sadeghi H, Mostafazadeh M, Sadeghi H, Naderian M, Barmak MJ, Talebianpoor MS, et al. In vivo anti-inflammatory properties of aerial parts of Nasturtium officinale. Pharm Biol 2014;52(2):169-174.

DOI: 10.3109/13880209.2013.821138.

Kandhare AD, Bodhankar SL, Mohan V, Thakurdesai PA. Effect of glycosides based standardized fenugreek seed extract in bleomycin-induced pulmonary fibrosis in rats: decisive role of Bax, Nrf2, NF-κB, Muc5ac, TNF-α and IL-1β. Chem Biol Interact. 2015;237:151-165.

DOI: 10.1016/j.cbi.2015.06.019.

Nikbakht J, Hemmati AA, Arzi A, Mansouri MT, Rezaie A, Ghafourian M. Protective effect of gallic acid against bleomycin-induced pulmonary fibrosis in rats. Pharmacol Rep. 2015;67(6):1061-1067.

DOI: 10.1016/j.pharep.2015.03.012.

Sadeghi H, Jahanbazi F, Sadeghi H, Omidifar N, Alipoor B, Kokhdan EP, et al. Metformin attenuates oxidative stress and liver damage after bile duct ligation in rats. Res Pharm Sci. 2019;14(2):122-129.

DOI: 10.4103/1735-5362.253359.

Arya A, Azarmehr N, Mansourian M, Doustimotlagh AH. Inactivation of the superoxide dismutase by malondialdehyde in the nonalcoholic fatty liver disease: a combined molecular docking approach to clinical studies. Arch Physiol Biochem. 2019:1-8.

DOI: 10.1080/13813455.2019.1659827.

Mansourian M, Sadeghi H, Doustimotlagh AH. Activation of the glutathione peroxidase by metformin in the bile-duct ligation-induced liver injury: in vivo combined with molecular docking studies. Curr Pharm Des. 2018;24(27):3256-3263.

DOI: 10.2174/1381612824666181003114108.

Ahluwalia N, Shea BS, Tager AM. New therapeutic targets in idiopathic pulmonary fibrosis. Aiming to rein in runaway wound-healing responses. Am J Respir Crit Care Med. 2014;190(8):867-878.

DOI: 10.1164/rccm.201403-0509PP.

Guan R, Wang X, Zhao X, Song N, Zhu J, Wang J, et al. Emodin ameliorates bleomycin-induced pulmonary fibrosis in rats by suppressing epithelial-mesenchymal transition and fibroblast activation. Sci Rep. 2016;6:35696,1-14.

DOI: 10.1038/srep35696.

Zaafan MA, Zaki HF, El-Brairy AI, Kenawy SA. Pyrrolidinedithiocarbamate attenuates bleomycin-induced pulmonary fibrosis in rats: modulation of oxidative stress, fibrosis, and inflammatory parameters. Exp Lung Res. 2016;42(8-10):408-416.

DOI: 10.1080/01902148.2016.1244578.

Azarmehr N, Afshar P, Moradi M, Sadeghi H, Sadeghi H, Alipoor B, et al. Hepatoprotective and antioxidant activity of watercress extract on acetaminophen-induced hepatotoxicity in rats. Heliyon. 2019;5(7):e02072,1-5.

DOI: 10.1016/j.heliyon.2019.e02072.

Nili-Ahmadabadi A, Alibolandi P, Ranjbar A, Mousavi L, Nili-Ahmadabadi H, Larki-Harchegani A, et al. Thymoquinone attenuates hepatotoxicity and oxidative damage caused by diazinon: an in vivo study. Res Pharm Sci. 2018;13(6):500-508.

DOI: 10.4103/1735-5362.245962.

Fahlyani BK, Behzad-Behbahani A, Taghavi SA, Farhadi A, Salehi S, Adibzadeh S, et al. Development of an in-house taqman real time RT-PCR assay to quantify hepatitis C virus RNA in serum and peripheral blood mononuclear cells in patients with chronic hepatitis C virus infection. Hepat Mon. 2015;15(8):e28895,1-6.

DOI: 10.5812/hepatmon.28895.

El-Khouly D, El-Bakly WM, Awad AS, El-Mesallamy HO, El-Demerdash E. Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced oxidative stress and activation of nuclear factor Kappa-B in rats. Toxicology. 2012;302(2-3):106-113.

DOI: 10.1016/j.tox.2012.09.001.

Coward WR, Saini G, Jenkins G. The pathogenesis of idiopathic pulmonary fibrosis. Ther Adv Respir Dis. 2010;4(6):367-388.

DOI: 10.1177/1753465810379801.

Soskić SS, Dobutović BD, Sudar EM, Obradović MM, Nikolić DM, Djordjevic JD, et al. Regulation of inducible nitric oxide synthase (iNOS) and its potential role in insulin resistance, diabetes and heart failure. Open Cardiovasc Med J. 2011;5:153-163.

DOI: 10.2174/1874192401105010153.

Abuelezz SA, Hendawy N, Osman WM. Aliskiren attenuates bleomycin-induced pulmonary fibrosis in rats: focus on oxidative stress, advanced glycation end products, and matrix metalloproteinase-9. N-S Arch Pharmacol. 2016;389:897-909.

DOI: 10.1007/s00210-016-1253-3.

Kalayarasan S, Sriram N, Sudhandiran G. Diallyl sulfide attenuates bleomycin-induced pulmonary fibrosis: critical role of iNOS, NF-κB, TNF-α and IL-1β. Life Sci. 2008;82(23-24):1142-1153.

DOI: 10.1016/j.lfs.2008.03.018.

Bahramikia S, Yazdanparast R. Antioxidant efficacy of Nasturtium officinale extracts using various in vitro assay systems. J Acupunct Meridian Stud. 2010;3(4):283-290.

DOI: 10.1016/S2005-2901(10)60049-0.

Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis. 2005;15(4):316-328.

DOI: 10.1016/j.numecd.2005.05.003.

Boligon AA, Janovik V, Boligon AA, Pivetta CR, Pereira RP, Rocha JBTd, et al. HPLC analysis of polyphenolic compounds and antioxidant activity in Nasturtium officinale. Int J Food Prop. 2013;16(1):61-69.

DOI: 10.1080/10942912.2010.528111.

Shahani S, Behzadfar F, Jahani D, Ghasemi M, Shaki F. Antioxidant and anti-inflammatory effects of Nasturtium officinale involved in attenuation of gentamicin-induced nephrotoxicity. Toxicol Mech Methods. 2017;27(2):107-114.

DOI: 10.1080/15376516.2016.1258748.


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