Journal
FREE RADICAL RESEARCH
Volume 52, Issue 4, Pages 402-414Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10715762.2018.1437914
Keywords
(+)-Catechin hydrate; monocrotaline; HSOS; Nrf2; Keap1
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Hepatic sinusoidal obstruction syndrome (HSOS) is a rare and life-threatening liver disease. (+)-Catechin is a natural dietary flavonol with high antioxidant capacity. This study aims to investigate the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant signalling pathway in the protection of (+)-catechin hydrate (CAT) against monocrotaline (MCT)-induced HSOS. Results of serum alanine/aspartate aminotransferases (ALT/AST) activities, total bilirubin (TBil) and bile acids (TBA) amounts, liver histological observation, scanning electron microscope evaluation, and hepatic metalloproteinase-9 (MMP-9) expression all demonstrated the protection of CAT against MCT-induced HSOS in rats. CAT attenuated MCT-induced liver oxidative injury in rats and the formation of cellular reactive oxygen species (ROS) in human hepatic sinusoidal endothelial cells (HHSECs). CAT-enhanced Nrf2 nuclear translocation in livers from MCT-treated rats and in HHSECs treated with ma, and further increased the expression of Nrf2-dependent genes including catalytic or modify subunit of glutamate-cysteine ligase (GCLC/GCLM), haem oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). Moreover, GCL inhibitor L-buthionine-(S, R)-sulfoximine (BSO), NQO1 inhibitor diminutol (Dim), and HO-1 inhibitor zinc protoporphyrin (ZnPP) all abrogated CAT-provided the protection against MCT-induced cytotoxicity in HHSECs. The results of molecular docking analysis indicated the potential interaction of CAT with the Nrf2-binding site in kelch-like ECH-associated protein-1 (Keap1) protein. In summary, this study demonstrated the critical involvement of Nrf2 antioxidant signalling pathway in CAT-provided the protection against MCT-induced HSOS.
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