4.7 Article

Quercetin and baicalein suppress monocrotaline-induced hepatic sinusoidal obstruction syndrome in rats

Journal

EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 795, Issue -, Pages 160-168

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2016.12.015

Keywords

Sinusoidal obstruction syndrome; TLRs/NF kappa B; Egr1; Nrf2; MAPKs; PI3K

Funding

  1. National Natural Science Foundation of China [81322053, 81573679]
  2. State major science and technology special projects [2015ZX09501004-002-002]
  3. Shu Guang project - Shanghai Municipal Education Commission
  4. Shanghai Education Development Foundation [13SG43]

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Hepatic sinusoidal obstruction syndrome (SOS) is a rare liver disease with considerable mortality. This study is designed to observe the protection of quercetin and baicalein against monocrotaline (MCP)-induced SOS in rats and its engaged mechanism. Rats were pre-administrated with MGT (90 mg/kg) to induce SOS, and 6, 30 h later were orally given with quercetin and baicalein (40 mg/kg) twice. Results of detecting rats with liver ascites, measuring serum transaminases, total bilirubin (TBil) and bile acids (TBA), analyzing blood cells, liver histological evaluation and scanning electron microscope observation all demonstrated the detoxification of quercetin and baicalein against MCT-induced SOS in rats. Quercetin and baicalein reduced the increased metalloproteinase-9 (MMP-9) expression, liver myeloperoxidase (MPO) activity, toll-like receptor (TLR)-2,3,6,9 expression and nuclear factor B-K (NFKB) transcriptional activation induced by MCT. Quercetin and baicalein reduced MCT-induced nuclear translocation of early growth responsel (Egrl) and increased expression of Serpinel and tissue factor (TF). Quercetin and baicalein reduced MCT-induced increased liver malondialdehyde (MDA) amount and enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Quercetin and baicalein also abrogated MCP -induced activation of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K) signaling cascades. In conclusion, this study demonstrated the protection of quercetin and baicalein against MCF-induced SOS in rats, indicating the potential application of them for the treatment of SOS in clinic. Transcriptional factor NFKB, Egrl and Nrf2-regulated inflammation, coagulation-fibrinolysis and antioxidant, and PI3K and MAPKs signaling, cascades are all involved such protection.

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