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http://dx.doi.org/10.3831/KPI.2018.21.032

Thymoquinone Prevents Myocardial and Perivascular Fibrosis Induced by Chronic Lipopolysaccharide Exposure in Male Rats - Thymoquinone and Cardiac Fibrosis -  

Asgharzadeh, Fereshteh (Neurogenic inflammation research center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences)
Bargi, Rahimeh (Neurogenic inflammation research center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences)
Beheshti, Farimah (Department of Basic Sciences and Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences)
Hosseini, Mahmoud (Neurocognitive Research Center, School of Medicine, Mashhad University of Medical Sciences)
Farzadnia, Mehdi (Departments of Pathology, School of Medicine, Mashhad University of Medical Sciences)
Khazaei, Majid (Neurogenic inflammation research center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences)
Publication Information
Journal of Pharmacopuncture / v.21, no.4, 2018 , pp. 284-293 More about this Journal
Abstract
Objectives: Thymoquinone (TQ) is one of the active ingredients of herbal plants such as Nigella sativa L. (NS) which has beneficial effects on the body. The beneficial effects of TQ on the cardiovascular system have reported. This study aimed to investigate the effect of TQ on cardiac fibrosis and permeability, serum and tissue concentration of inflammatory markers and oxidative stress status in chronic lipopolysaccharide exposure in male rats. Methods: Seventy male Wistar rats were randomly divided into five groups as follows: (1) control; (2) LPS (1 mg/kg/day); (3-5) LPS + TQ with three doses of 2, 5 and 10 mg/kg (n=14 in each group). After 3 weeks, serum and cardiac levels of $IL-1{\beta}$, $TNF-{\alpha}$ and nitric oxide (NO) metabolites, and cardiac levels of malondialdehyde (MDA), total thiol groups, catalase (CAT) and superoxide dismutase (SOD) activities, permeability of heart tissue (evaluated by Evans blue dye method) and myocardial fibrosis were determined, histologically. Results: LPS administration induced myocardial and perivascular fibrosis and increased cardiac oxidative stress (MDA), inflammatory markers and heart permeability, while, reduced anti-oxidative enzymes (SOD and CAT) and the total thiol group. Administration of TQ significantly attenuated these observations. Conclusion: TQ improved myocardial and perivascular fibrosis through suppression of chronic inflammation and improving oxidative stress status and can be considered for attenuation of cardiac fibrosis in conditions with chronic low-grade inflammation.
Keywords
thymoquinone; inflammation; cardiac; fibrosis;
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1 Ahmad I, Muneer KM, Tamimi IA, Chang ME, Ata MO, Yusuf N. Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome. Toxicol Appl Pharmacol. 2013;270(1):70-6.   DOI
2 Alimohammadi S, Hobbenaghi R, Javanbakht J, Kheradmand D, Mortezaee R, Tavakoli M, et al. Protective and antidiabetic effects of extract from Nigella sativa on blood glucose concentrations against streptozotocin (STZ)-induced diabetic in rats: an experimental study with histopathological evaluation. Diagn Pathol. 2013;8:137.   DOI
3 Asgharzadeh F, Rouzbahani, R, Khazaei, M. Chronic low-grade inflammation: Etiology and its effects Journal of Isfahan Medical School. 2016;34(379):408-21.
4 Bai T, Lian LH, Wu YL, Wan Y, Nan JX. Thymoquinone attenuates liver fibrosis via PI3K and TLR4 signaling pathways in activated hepatic stellate cells. Int Immunopharmacol. 2013;15(2):275-81.   DOI
5 Bargi R, Asgharzadeh F, Beheshti F, Hosseini M, Sadeghnia HR, Khazaei M. The effects of thymoquinone on hippocampal cytokine level, brain oxidative stress status and memory deficits induced by lipopolysaccharide in rats. Cytokine. 2017;96:173-84.   DOI
6 Darakhshan S, Bidmeshki Pour A, Hosseinzadeh Colagar A, Sisakhtnezhad S. Thymoquinone and its therapeutic potentials. Pharmacol Res. 2015;95-96:138-58.   DOI
7 Doi K, Leelahavanichkul A, Yuen PS, Star RA. Animal models of sepsis and sepsis-induced kidney injury. J Clin Invest. 2009;119(10):2868-78.   DOI
8 El-Mahmoudy A, Matsuyama H, Borgan MA, Shimizu Y, El-Sayed MG, Minamoto N, et al. Thymoquinone suppresses expression of inducible nitric oxide synthase in rat macrophages. Int Immunopharmacol. 2002;2(11):1603-11.   DOI
9 Gholamnezhad Z, Havakhah S, Boskabady MH. Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review. J Ethnopharmacol. 2016;190:372-86.   DOI
10 Ghazwani M, Zhang Y, Gao X, Fan J, Li J, Li S. Anti-fibrotic effect of thymoquinone on hepatic stellate cells. Phytomedicine. 2014;21(3):254-60.   DOI
11 Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev. 2004;18(18):2195-224.   DOI
12 Helmersson J, Vessby B, Larsson A, Basu S. Association of type 2 diabetes with cyclooxygenase-mediated inflammation and oxidative stress in an elderly population. Circulation. 2004;109(14):1729-34.   DOI
13 Hosseinzadeh H, Sadeghnia HR. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci. 2005;8(3):394-9.
14 Nematollahi S, Nematbakhsh M, Haghjooyjavanmard S, Khazaei M, Salehi M. Inducible nitric oxide synthase modulates angiogenesis in ischemic hindlimb of rat. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009;153(2):125-9.   DOI
15 Hotamisligil GS, Erbay E. Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol. 2008;8(12):923-34.   DOI
16 Janero DR. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med. 1990;9(6):515-40.   DOI
17 Lew WY, Bayna E, Molle ED, Dalton ND, Lai NC, Bhargava V, et al. Recurrent exposure to subclinical lipopolysaccharide increases mortality and induces cardiac fibrosis in mice. PLoS One. 2013;8(4):e61057.   DOI
18 Khazaei M, Nematbakhsh M. Coronary vascular and aortic endothelial permeability during estrogen therapy: a study in DOCA-salt hypertensive ovariectomized rats. Physiol Res. 2004;53(6):609-14.
19 Ko HJ, Oh SK, Jin JH, Son KH, Kim HP. Inhibition of Experimental Systemic Inflammation (Septic Inflammation) and Chronic Bronchitis by New Phytoformula BL Containing Broussonetia papyrifera and Lonicera japonica. Biomol Ther (Seoul). 2013;21(1):66-71.   DOI
20 Leon CG, Tory R, Jia J, Sivak O, Wasan KM. Discovery and development of toll-like receptor 4 (TLR4) antagonists: a new paradigm for treating sepsis and other diseases. Pharm Res. 2008;25(8):1751-61.   DOI
21 Li Q, Verma IM. NF-kappaB regulation in the immune system. Nat Rev Immunol. 2002;2(10):725-34.   DOI
22 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(5):431-6.   DOI
23 Tahergorabi Z, Khazaei M. The relationship between inflammatory markers, angiogenesis, and obesity. ARYA Atheroscler. 2013;9(4):247-53.
24 Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol. 2007;292(1):C82-97.
25 Min HY, Song SH, Lee B, Kim S, Lee SK. Inhibition of lipopolysaccharide-induced nitric oxide production by antofine and its analogues in RAW 264.7 macrophage cells. Chem Biodivers. 2010;7(2):409-14.   DOI
26 Norouzi F, Abareshi A, Asgharzadeh F, Beheshti F, Hosseini M, Farzadnia M, et al. The effect of Nigella sativa on inflammation-induced myocardial fibrosis in male rats. Res Pharm Sci. 2017;12(1):74-81.   DOI
27 Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol (1985). 2005;98(4):1154-62.   DOI
28 Elmi S, Sallam NA, Rahman MM, Teng X, Hunter AL, Moien-Afshari F, et al. Sulfaphenazole treatment restores endothelium-dependent vasodilation in diabetic mice. Vascul Pharmacol. 2008;48(1):1-8.   DOI
29 Tekeoglu I, Dogan A, Demiralp L. Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat models. Phytother Res. 2006;20(10):869-71.   DOI
30 Sallam N, Khazaei M, Laher I. Effect of moderate-intensity exercise on plasma C-reactive protein and aortic endothelial function in type 2 diabetic mice. Mediators Inflamm. 2010;149678(10):2.
31 Wang Y, Gao H, Zhang W, Fang L. Thymoquinone inhibits lipopolysaccharide-induced inflammatory mediators in BV2 microglial cells. Int Immunopharmacol. 2015;26(1):169-73.   DOI
32 Woo CC, Kumar AP, Sethi G, Tan KH. Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol. 2012;83(4):443-51.   DOI
33 Yasuda S, Lew WY. Lipopolysaccharide depresses cardiac contractility and beta-adrenergic contractile response by decreasing myofilament response to Ca2+ in cardiac myocytes. Circ Res. 1997;81(6):1011-20.   DOI