Abstract
Objectives
Curcumin is described as an antioxidant, hepato-protective and antifibrotic in liver fibrosis, although its mechanism is still not known. One of the models of the chronic liver disease stemming from oxidative stress and the generation of free radical has been considered to be bile duct ligation (BDL). Paraoxonase 1 (PON1) is a prominent antioxidant enzyme. Therefore, the objective of the present research is to assess the effects of curcumin on upregulation of PON1 in BDL rats.
Methods
As predicted, the rats have been divided into the four groups of Sham, Sham + Cur (curcumin), BDL and BDL + Cur. We evaluated the efficacy of curcumin (100 mg/kg/day) on protein and gene expression of PON1 and regulatory genes contributed to the gene expression PON1 such as Sp1, PKCα, SREBP-2, AhR, JNK and regulation PON1 activity gene expression of Apo A1.
Results
Curcumin attenuated alterations in liver histology, hepatic enzymes and the mRNA expression of fibrotic markers (p<0.05). In addition, curcumin increased significantly mRNA, protein expression of PON1 and mRNA of the genes that are contributed to the expression of PON1 such as Sp1, PKCα, SREBP-2, AhR, JNK and increased PON1 activity through upregulation of Apo A1 (p<0.05).
Conclusions
Cirrhosis progression may be inhibited by treatment with curcumin through the increased influence the expression and activity of PON1.
Funding source: Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
Acknowledgments
The researchers would like to appreciate Zeinab Hafizi and Maryam Ajdari for their help in performing the research.
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Research funding: The present research has been financial supported by Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Author contributions: A.M.: Contributed to conception and design. A.Kh., A.E., Z.Gh.: Conducted molecular experiments and RT-qPCR analysis. D.J., H.R.Y., A.K: Contributed to all experimental work, data and statistical analysis and interpretation of data. A.M., A.Kh.: Revising it critically for important intellectual content. All authors performed editing and approving the final version of this paper for submission, also participated in the finalization of the manuscript and approved the final draft.
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Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication. The authors state no conflict of interest.
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Ethical approval: Animal care protocols that were confirmed by the Ethics Committee on Animal Welfare were applied in all experiments based on the guidelines declared by Shahid Sadoughi Univ. of Medical Sciences and Health Services (IR.SSU.MEDICINE.REC.1394.401).
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