Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Dec;22(12):1483-1492.
doi: 10.22038/IJBMS.2019.14069.

Ameliorative effects of silymarin on HCl-induced acute lung injury in rats; role of the Nrf-2/HO-1 pathway

Rasha F Ahmed  1 , Rabab A Moussa  2 , Reda S Eldemerdash  3 , Mahmoud M Zakaria  3 , Seham A Abdel-Gaber  4
Affiliations

Ameliorative effects of silymarin on HCl-induced acute lung injury in rats; role of the Nrf-2/HO-1 pathway

Rasha F Ahmed et al. Iran J Basic Med Sci. 2019 Dec.

Abstract

Objectives: Aspiration is a common cause of acute lung injury (ALI), which lacks an effective treatment. Inflammation and oxidative stress play key roles in ALI development. Silymarin is an active extract of Silybum marianum plant seeds (milk thistle). Silymarin has potent anti-inflammatory and antioxidant effects; however its role in aspiration induced ALI has not been investigated. The aim of this study is to investigate the role of silymarin in the treatment of hydrochloric acid (HCl) aspiration induced ALI and explores its mechanisms of action.

Materials and methods: The study included three groups of rats: Control non-treated group, ALI group (intra-tracheal HCl injected), and silymarin treated ALI group. White blood cells (WBCs) with differential count, oxidative stress parameters, B-cell lymphoma 2 (Bcl-2), transforming growth factor-beta (TGF-β), cyclooxygenase 2 (COX-2), nuclear factor erythroid 2-related factor-2 (Nrf-2), and heme oxygenase-1 (HO-1) were investigated. Lung tissue histopathology and immunohistochemical expression of survivin and proliferating cell nuclear antigen (PCNA) were also examined.

Results: The results of the study showed that HCL caused histopathological changes in ALI with leukocytopenia and increased oxidative stress biomarkers. It increased TGF-β, up-regulated mRNA expression of COX-2, Nrf-2, and HO-1 and increased survivin and PCNA but decreased Bcl-2. Silymarin ameliorated the histopathological lung injury with further up-regulation of Nrf-2 and HO-1 mRNA and decreased the inflammatory and fibrotic parameters together with up-regulation of the anti-apoptotic and the proliferation parameters.

Conclusion: The protective effect of silymarin against ALI is mediated by Nrf-2/HO-1 pathway with subsequent antioxidant, anti-inflammatory, antiapoptotic, and proliferating activities.

Keywords: Acute lung injury; Fibrosis; Heme oxygenase-1; Silymarin; Survivin.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
Effect of silymarin on Bcl-2 detection by flow cytometry
Figure 2
Figure 2
Effect of silymarin on transforming growth factor-beta (TGF-β) detection by flow cytometry
Figure 3
Figure 3
Relative mRNA expression by polymerase chain reaction (PCR) relative to that of the normal control group
Figure 4
Figure 4
Histopathology of lung tissue
Figure 5.
Figure 5.
Immunohistochemical staining of lung tissue survivin (magnification X200)
Figure 6
Figure 6
Immunohistochemical staining of lung tissue proliferating cell nuclear antigen (PCNA) (magnification X200)
See this image and copyright information in PMC

References

    1. Qing R, Huang Z, Tang Y, Xiang Q, Yang F. Cordycepin alleviates lipopolysaccharide-induced acute lung injury via Nrf2/HO-1 pathway. Int Immunopharmacol. 2018;60:18–25. - PubMed
    1. Qian L, Zhao Y, Guo L, Li S, Wu X. Activating transcription factor 3 (ATF3) protects against lipopolysaccharide-induced acute lung injury via inhibiting the expression of TL1A. J Cell Physiol. 2017;232:3727–3734. - PubMed
    1. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet. 1967;2:319–323. - PubMed
    1. Tsushima K, King LS, Aggarwal NR, De Gorordo A, D’Alessio FR, Kubo K. Acute lung injury review. Internal medicine. 2009;48:621–630. - PubMed
    1. Reiss LK, Uhlig U, Uhlig S. Models and mechanisms of acute lung injury caused by direct insults. Eur J Cell Biol. 2012;91:590–601. - PubMed

LinkOut - more resources