Journal of Pharmacopuncture (대한약침학회지)

KOREAN PHARMACOPUNCTURE INSTITUTE (대한약침학회)
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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)
  • Received : 2017.05.09
  • Accepted : 2018.11.14
  • Published : 2018.12.31
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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

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Figure 1 Serum (A) and heart (B) IL-1β levels in experimental groups.

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Figure 1 Serum (A) and heart (B) IL-1β levels in experimental groups.

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Figure 2 Serum (A) and heart (B) nitrite concentrations.

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Figure 2 Serum (A) and heart (B) nitrite concentrations.

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Figure 3 Comparison of MDA (A) and total thiol concentration (B) in heart homogenate in experimental groups.

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Figure 3 Comparison of MDA (A) and total thiol concentration (B) in heart homogenate in experimental groups.

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Figure 5 H&E staining of left ventricles in control (A) and LPS (B) groups. Arrows indicate infiltration of inflammatory cells and disarrangement of fibers. TQ reduced infiltration of inflammatory cells in the heart tissue (C-E: TQ 2, 5, and 10 mg/kg; respectively). n=6 in each group.

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Figure 5 H&E staining of left ventricles in control (A) and LPS (B) groups. Arrows indicate infiltration of inflammatory cells and disarrangement of fibers. TQ reduced infiltration of inflammatory cells in the heart tissue (C-E: TQ 2, 5, and 10 mg/kg; respectively). n=6 in each group.

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Figure 4 Permeability of heart tissue in experimental groups.

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Figure 4 Permeability of heart tissue in experimental groups.

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Figure 6 Masson trichrome staining of left ventricular wall fibrosis. A: control; B: LPS group shows more collagen deposition (Blue color indicates collagen fibers characterized by black arrow). Administration of TQ improved cardiac fibrosis dose dependently. Cardiac fibrosis expressed as higher collagen content (%) in LPS group compare to control which improved by TQ administration (F).

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Figure 6 Masson trichrome staining of left ventricular wall fibrosis. A: control; B: LPS group shows more collagen deposition (Blue color indicates collagen fibers characterized by black arrow). Administration of TQ improved cardiac fibrosis dose dependently. Cardiac fibrosis expressed as higher collagen content (%) in LPS group compare to control which improved by TQ administration (F).

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Figure 7 Perivascular fibrosis around left anterior descending coronary artery (black arrows) stained by Masson trichrome. Blue color indicates collagen deposition. A: control; B: LPS; C-E: TQ by doses of 2, 5 and 10 mg/kg; respectively.

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Figure 7 Perivascular fibrosis around left anterior descending coronary artery (black arrows) stained by Masson trichrome. Blue color indicates collagen deposition. A: control; B: LPS; C-E: TQ by doses of 2, 5 and 10 mg/kg; respectively.

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