Bear bile powder attenuates senecionine-induced hepatic sinusoidal obstruction syndrome in mice / 中国天然药物

Hepatic sinusoidal obstruction syndrome (HSOS) via exposure to pyrrolizidine alkaloids (PAs) is with high mortality and there is no effective treatment in clinics. Bear bile powder (BBP) is a famous traditional animal drug for curing a variety of hepatobiliary diseases such as cholestasis, inflammation, and fibrosis. Here, we aim to evaluate the protective effect of BBP against HSOS induced by senecionine, a highly hepatotoxic PA compound. Our results showed that BBP treatment protected mice from senecionine-induced HSOS dose-dependently, which was evident by improved liver histology including reduced infiltration of inflammatory cells and collagen positive cells, alleviated intrahepatic hemorrhage and hepatic sinusoidal endothelial cells, as well as decreased conventional serum liver function indicators. In addition, BBP treatment lowered matrix metalloproteinase 9 and pyrrole-protein adducts, two well-known markers positively associated with the severity of PA-induced HSOS. Further investigation showed that BBP treatment prevents the development of liver fibrosis by decreasing transforming growth factor beta and downstream fibrotic molecules. BBP treatment also alleviated senecionine-induced liver inflammation and lowered the pro-inflammatory cytokines, in which tauroursodeoxycholic acid played an important role. What's more, BBP treatment also decreased the accumulation of hydrophobic bile acids, such as cholic acid, taurocholic acid, glycocholic acid, as well. We concluded that BBP attenuates senecionine-induced HSOS in mice by repairing the bile acids homeostasis, preventing liver fibrosis, and alleviating liver inflammation. Our present study helps to pave the way to therapeutic approaches of the treatment of PA-induced liver injury in clinics.

Gynura segetum induces hepatic sinusoidal obstruction syndrome in mice by impairing autophagy

ABSTRACT Purpose: To investigate the underlying mechanism of hepatic sinusoidal obstruction syndrome (HSOS) induced by Gynura segetum by measuring autophagy in mouse models. Methods: The model group was administered G. segetum (30 g/kg/d) by gavage, while the normal control group was administered an equal volume of saline daily for five weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic histopathological examinations, and Masson staining were performed to evaluate liver injury. Liver intercellular adhesion molecule-1 (ICAM-1) and P-selectin were evaluated by immunohistochemistry. Hepatocellular apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Protein expression levels of autophagy markers were measured using Western blot analysis. Results: Gynura segetum was found to significantly induce liver injury compared with control mice, as evidenced by the increase of serum transaminases, a decrease in triglyceride levels, and histopathological changes in mice. Gynura segetum remarkably induced hepatocellular apoptosis and upregulated the expressions of ICAM-1 and P-selectin and also downregulated the protein expression levels of LC3, Atg12 and cytoplasmic polyadenylation element binding protein. Conclusions: Our results suggested that G. segetum induced liver injury with HSOS, and it was partly due to its ability to impair the autophagy pathway.

Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation

This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis.

Sinusoidal obstruction syndrome after oxaliplatin-based chemotherapy

No abstract available.

outbreak of veno-occlusive disease of the liver in northern Iraq

This paper describes an outbreak of veno-occlusive disease of the liver which occurred in Mosul, northern Iraq in 1994. It was caused by the consumption of wheat accidentally contaminated with Senecio seeds which produced toxic pyrrolizidine alkaloids. The outbreak involved 14 people [eight males and six females] who were members of three Bedouin families. Half of the cases were under the age of 15 years. The striking clinical features were abdominal pain, rapidly filling ascites and hepatomegaly. Two deaths occurred during hospitalization, with an estimated case fatality rate of 14%

Diagnóstico do bloqueio ao efluxo venoso do fígado pela análise bioquímica do efluente hepático pré-revascularizaçäo do órgäo no transplante de fígado / Diagnosis of blockade liver venous outflow by biochemical analisys of hepatic effluent revascularization of the organ in liver transplant

O objetivo do presente trabalho é avaliar as alteraçöes enzimáticas do efluente hepático e a funçäo mitocondrial do fígado como indicadores da síndrome de bloqueio ao efluxo venoso do fígado (BEVF). Foram estudados 14 cäes mestiços de ambos os sexos com peso variando de 16 a 20 Kg, submetidos a transplante ortotópico de fígado sendo sete doadores e sete receptores. Após a anastomose da veia cava supra-hepática perfundiu-se o fígado com 300ml de soluçäo de cloreto de sódio a 0,9//) (SF) pela veia porta, colhendo-se o efluente hepático (EH) pela veia cava infra-hepática em 4 frascos de 20ml, para dosagens de DHL, AST e ALT. Amostras de tecido hepático foram colhidas no início da operaçäo do doador (D1) imediatamente antes do implante (D@), 15 minutos (R1) e 60 minutos (R2) após a reperfusäo hepática no receptor. Nos animais com BEVF os níveis de DHL, ALT e AST no EH foram significativamente superiores aos controles. A respiraçäo mitocondrial hepática em todos os tempos estudados, foi significativamente maior e efetiva nos controles do que nos animais com BEVF. O BEVF foi confirmado pelo exame anatomopatológico que mostrou necrose hepatocelular, alargamento sinusoidal e destruiçäo da veia centro-lobular