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The effect of capillarisin on glycochenodeoxycholic acid-induced apoptosis and heme oxygenase-1 in rat primary hepatocytes

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Abstract

The accumulation of hydrophobic bile acids plays a role in the induction of apoptosis and necrosis of hepatocytes during cholestasis. Glycochenodeoxycholate acid (GCDC) triggers a rapid oxidative stress response as an event of glutathione (GSH) depletion and nuclear factor kappa B (NF-κB) activation. We therefore investigated whether the bioactivity of the antioxidant capillarisin (Cap) prevents GCDC-induced hepatocyte damage. Isolated rat hepatocytes were co-incubated with 100 μM GCDC and 0.5 mg/ml Cap for 4 h. GSH depletion and thiobarbituric acid-reactive substances (TBARS, measure of lipid peroxidation) increased after GCDC exposure, but were markedly suppressed by Cap treatment. Cap protected hepatocytes from a GCDC-induced increase in reactive oxygen species (ROS) generation and mitochondrial membrane potential induction, as measured by flow cytometry analysis. In addition, Cap was shown to inhibit GCDC-mediated NF-κB activation by using electrophoretic mobility shift assays (EMSA). In contrast to GCDC, Cap not only significantly decreased cytochrome c release and caspase-3 enzyme activity, but also suppressed heme oxygenase-1 protein and mRNA expression in hepatocytes. These results demonstrate that Cap function as an antioxidant reduced hepatocyte injury caused by hydrophobic bile acids, perhaps by preventing generation of ROS and release of cytochrome c, thereby minimizing hepatocytes apoptosis.

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Acknowledgments

This study was supported by the following: Grant nos. CCMP95-RD-207 from the Committee on Chinese Medicine and Pharmacy, Department of Health, NSC96-2320-B-182-021-MY2 from the National Science Council, Taiwan, and CMRPD160201 from the Chang Gung Memorial Hospital, Taoyuan, Taiwan.

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Authors and Affiliations

  1. Graduate Institute of Traditional Chinese Medicine, Chang Gung University, No. 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, 333, Taiwan, R.O.C.

    Tzung-Yan Lee, Fang-Yu Chen & Hen-Hong Chang

  2. Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, R.O.C.

    Hen-Hong Chang

  3. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.

    Han-Chieh Lin

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  1. Tzung-Yan Lee
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Correspondence to Tzung-Yan Lee.

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Lee, TY., Chen, FY., Chang, HH. et al. The effect of capillarisin on glycochenodeoxycholic acid-induced apoptosis and heme oxygenase-1 in rat primary hepatocytes. Mol Cell Biochem 325, 53–59 (2009). https://doi.org/10.1007/s11010-008-0019-8

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