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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2016

Open Access 01-12-2016 | Research

The fibrolytic potentials of vitamin D and thymoquinone remedial therapies: insights from liver fibrosis established by CCl4 in rats

Authors: Abdelghany Hassan Abdelghany, Mohammad A. BaSalamah, Shakir Idris, Jawwad Ahmad, Bassem Refaat

Published in: Journal of Translational Medicine | Issue 1/2016

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Abstract

Background

Vitamin D (VitD) and thymoquinone (TQ) are nutraceutical agents with well-known immunomodulatory and hepatoprotective properties. This study measured whether VitD and TQ, individually or combined, could have direct fibrolytic activities and/or enhanced performance during remedial treatment of liver fibrosis established by CCl4 in rats.

Methods

Eighty five male Wistar rats were used as 10 negative controls (NC) and the remainders were distributed equally into 5 groups: short (S-PC) and long (L-PC) positive controls, TQ, VitD and VitD/TQ groups. CCl4 was injected for 7 weeks followed by a week of no intervention. TQ and/or VitD were given orally (3 days/week) from week 9 and euthanasia was at week 17 for all groups except the S-PC was at week 9. Following histopathological and digital image analyses, TGF-β1, IL-6, IL-10, IL-22 and MMP-9 were measured by ELISA in liver homogenates while the corresponding cytokine receptors were measured by immunohistochemistry. The mRNA expressions of all molecules were measured by quantitative RT-PCR.

Results

Fibrosis was evident in both PC-groups and was significantly more advanced in the L-PC than S-PC, reaching to cirrhosis. The concentrations of TGF-β1, IL-6, IL-22 and their receptors were significantly higher (P < 0.05) simultaneously with significantly lower (P < 0.05) concentrations of MMP-9, IL-10 and IL-10 receptors in the S-PC and L-PC than the NC-group. TQ and VitD monotherapies showed significantly less fibrosis than L-PC but were similar to S-PC. Both remedial monotherapies also resulted in significant decreases of TGF-β1, IL-6, IL-22 and their receptors together with significant increases of MMP-9 and IL-10 system compared with S-PC and L-PC groups. Interestingly, dual therapy resulted in the most significant improvement in fibrosis score and index, yet was significantly higher (P < 0.05) than the NC-group, and concurred with the utmost significant restorations of all candidate genes and proteins.

Conclusions

VitD and TQ exhibited comparable anti-fibrogenic effects and modulated several pro- and anti-fibrotic mediators. Additionally, VitD/TQ dual therapy alleviated the previously established liver fibrosis simultaneously with significantly enhanced actions at the molecular level. More studies are required to explorer the therapeutic value of TQ and VitD against liver fibrosis in human.
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Metadata
Title
The fibrolytic potentials of vitamin D and thymoquinone remedial therapies: insights from liver fibrosis established by CCl4 in rats
Authors
Abdelghany Hassan Abdelghany
Mohammad A. BaSalamah
Shakir Idris
Jawwad Ahmad
Bassem Refaat
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2016
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-016-1040-4

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