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[Protective effect of quercetin against immunological liver injury through activating Nrf2/ARE signaling pathway]
Caibing Wei1, Liandi Zhou1, Yuzhen Zhang2
1Research Center of Molecular Medicine and Cancer, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
Abstract:
Objective To observe the protective effect of quercetin against immunological liver injury induced by triptolide, and investigate the involvement of Nrf2/ARE signaling pathway in the protection. Methods Fifty C57BL/6J mice were randomly divided into five groups: control group, model group, (20, 50, 80) mg/kg quercetin pre-treatment groups. Each group included 10 mice. The mice were treated with different doses of quercetin once daily for consecutive 10 days. At the end of the experiment, triptolide (500 μg/kg) was given intragastrically to induce immunological liver injury in all groups except for the control group. Twenty-two hours later, the levels of serum ALT , AST were detected. The contents of GSH, SOD and MDA in liver tissue homogenates were measured through commercial kits. HE staining was performed to observe pathologic changes of the liver. The mRNA expressions of heme oxygenase-1 (HO-1), NQO1, glutamate-cysteine ligase catalytic subunit (GCLC) was tested by quantitative real-time PCR, and the protein expression of Nrf2 was detected by Western blotting. Results Compared with the model group, the serum activities of ALT and AST as well as MDA content remarkably decreased by the administration of quercetin (80 mg/kg), while GSH, SOD contents were elevated in liver tissues; pathologic changes of the liver was ameliorated evidently by quercetin; Nrf2 protein expression in the nucleus as well as mRNA expressions of HO-1, NQO1, GCLC increased. Moreover, the protective effect of 50 mg/kg quercetin was not as good as that of 80 mg/kg quercetin, and 20 mg/kg quercetin did little against the immunological liver injury. Conclusion High-dose quercetin can inhibit immunological liver injury induced by triptolide, and the mechanism may be associated with the activation of Nrf2/ARE signaling pathway.
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