(-)-Epicatechin attenuates hepatic sinusoidal obstruction syndrome by inhibiting liver oxidative and inflammatory injury
| العنوان: | (-)-Epicatechin attenuates hepatic sinusoidal obstruction syndrome by inhibiting liver oxidative and inflammatory injury |
|---|---|
| المؤلفون: | Zhengtao Wang, Yuchen Sheng, Zhanxia Hao, Lili Ji, Xiaoqi Jing, Zhenlin Huang, Jiaqi Zhang |
| المصدر: | Redox Biology Redox Biology, Vol 22, Iss, Pp-(2019) |
| بيانات النشر: | Elsevier, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Models, Molecular, MDA, malondialdehydeand, Nrf2, Nuclear factor erythroid 2-related factor 2, GSH, reduced glutathione, Clinical Biochemistry, Hepatic Veno-Occlusive Disease, Molecular Conformation, MPO, myeloperoxidase, HO-1, heme oxygenase 1, Pharmacology, HSOS, Biochemistry, Antioxidants, Catechin, Liver disease, chemistry.chemical_compound, H2DCFDA, 2′-7′-dichlorodihydrofluorescein diacetate, Mice, 0302 clinical medicine, lcsh:QH301-705.5, lcsh:R5-920, Monocrotaline, biology, (-)-Epicatechin, HSCT, hematopoietic stem-cell transplantation, EPI, (-)-epicatechin, TBA, bile acids, DILI, drug-induced liver injury, Liver, Myeloperoxidase, LPO, lipid peroxidation, Signal transduction, HSP60, heat shock protein 60, Inflammation Mediators, lcsh:Medicine (General), Oxidation-Reduction, Research Paper, Signal Transduction, ALT/AST, alanine/aspartate aminotransferases, MCT, monocrotaline, Bilirubin, TBil, total bilirubin, NF-E2-Related Factor 2, H&E, hematoxylin-eosin, HSOS, hepatic sinusoidal obstruction syndrome, Mice, Transgenic, Oxidative phosphorylation, Nrf2, 03 medical and health sciences, Structure-Activity Relationship, ROS, reactive oxygen species, Heat shock protein, Keap1, kelch-like ECH-associated protein-1, GST, glutathione-S-transferase, medicine, Animals, GCLC, catalytic subunit of glutamate-cysteine ligase, TALEN, transcription activator-like effector nucleases, HPAs, hepatotoxic pyrrolizidine alkaloids, MMP-9, metalloproteinase-9, GCLM, modify subunit of glutamate-cysteine ligase, Organic Chemistry, Chaperonin 60, medicine.disease, NQO1, NAD(P)H: quinone oxidoreductase 1, KEAP1, Rats, HSECs, hepatic sinusoidal endothelial cells, Disease Models, Animal, Oxidative Stress, 030104 developmental biology, NFκB, nuclear factor κB, lcsh:Biology (General), chemistry, i.g., intragastrical administration, biology.protein, MOF, multi-organ failure, NAFLD, nonalcoholic fatty liver disease, Reactive Oxygen Species, 030217 neurology & neurosurgery, TBIL, Biomarkers, NFκB |
| الوصف: | Hepatic sinusoidal obstruction syndrome (HSOS) is a rare liver disease with considerable morbidity and mortality. (-)-Epicatechin (EPI) is a natural flavonol. This study aims to investigate the protection of EPI against monocrotaline (MCT)-induced HSOS and its engaged mechanism. Results of serum alanine/aspartate aminotransferases (ALT/AST) activities, total bilirubin (TBil) and bile acids (TBA) amounts, liver histological evaluation, scanning electron microscope observation and hepatic metalloproteinase-9 (MMP-9) expression all demonstrated the protection by EPI against MCT-induced HSOS in rats. EPI attenuated liver oxidative injury induced by MCT. EPI enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the expression of its downstream antioxidant genes in rats. Molecular docking results implied the potential interaction of EPI with the Nrf2 binding site in kelch-like ECH-associated protein-1 (Keap1). The EPI-provided protection against MCT-induced HSOS was diminished in Nrf2 knock-out mice when mice were treated with MCT for 24 h but not for 48 h. However, EPI reduced the increased liver myeloperoxidase (MPO) activity, hepatic infiltration of immune cells, pro-inflammatory cytokines expression and nuclear factor κB (NFκB) activation in both wild-type and Nrf2 knock-out mice when mice were treated with MCT for 48 h. EPI reduced the elevated serum heat shock protein 60 (HSP60) content, and reversed the decreased mitochondria expression of HSP60 and Lon in livers from MCT-treated rats. Furthermore, the MCT-induced HSOS was markedly alleviated in mice treated with anti-HSP60 antibody. Taken together, this study demonstrates that EPI attenuates MCT-induced HSOS by reducing liver oxidative injury via activating Nrf2 antioxidant pathway and inhibiting liver inflammatory injury through abrogating NFκB signaling pathway initiated by HSP60. Graphical abstract Image 1 Highlights • EPI attenuates MCT-induced HSOS in rats. • EPI inhibits MCT induced liver oxidative injury in rats. • Nrf2 is important for the EPI-provided protection against MCT-induced HSOS. • EPI also abrogates MCT-induced liver inflammatory injury. • EPI reduced the release of HSP60. |
| اللغة: | English |
| تدمد: | 2213-2317 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::10399ed0ce5ab7a59c41310ef32ed9c1Test http://europepmc.org/articles/PMC6395886Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....10399ed0ce5ab7a59c41310ef32ed9c1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22132317 |
|---|