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Curcumin and hemopressin treatment attenuates cholestasis-induced liver fibrosis in rats: role of CB1 receptors

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Abstract

Curcumin exerts hepatoprotective effects via poorly defined mechanisms. Recently, some studies suggested that this effect was mediated by antagonizing CB1 receptors in hepatic stellate cells. The current study aimed to investigate whether CB1 antagonist, hemopressin, could potentiate the hepatoprotective effect of curcumin, in comparison with silymarin in bile duct-ligated (BDL) rats. Curcumin and hemopressin each alone and in combination ameliorated biochemical and structural fibrotic injury, and downregulated cyclooxygenase-2 (COX-2) and both mRNA and protein levels of nuclear factor kappa B (NF-κB) in fibrotic liver. In contrast to the previous studies, curcumin alone did not affect the gene expression of cannabinoid receptors. However, the combination of hemopressin and curcumin reduced the expression of CB1 in fibrotic liver. Surprisingly, silymarin upregulated CB2 receptors and downregulated CB1 at mRNA level more than all the administered drugs. Both curcumin and hemopressin each alone decreased lipid peroxidation product, malondialdehyde (MDA), while the combination increased the reduced glutathione content. All the administered drugs increased the hepatic antiapoptotic marker, Bcl2. Our study suggests that hemopressin potentiates the hepatoprotective effect of curcumin on fibrotic liver. We identified a new mechanism of the hepatoprotective effect of silymarin via modulation of cannabinoid receptors in fibrotic liver.

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Acknowledgments

The authors thank to Laila Rashed Biochemistry Department, Faculty of Medicine, Cairo University, for assistance in performing PCR technique and Zagazig University for financial support.

Authors’ contributions

M FM was responsible for study design and result analyses and wrote the article. SE was responsible for project designs and result analyses and wrote the article. AI performed the practical work. RH performed the histopathological studies.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt

    Sahar El Swefy & Amal Ibrahim

  2. Department of Histology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt

    Rehab A. Hasan

  3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt

    Mona F. Mahmoud

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  1. Sahar El Swefy
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  2. Rehab A. Hasan
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  3. Amal Ibrahim
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  4. Mona F. Mahmoud
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Correspondence to Mona F. Mahmoud.

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El Swefy, S., Hasan, R.A., Ibrahim, A. et al. Curcumin and hemopressin treatment attenuates cholestasis-induced liver fibrosis in rats: role of CB1 receptors. Naunyn-Schmiedeberg's Arch Pharmacol 389, 103–116 (2016). https://doi.org/10.1007/s00210-015-1181-7

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