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.

Megalocitose de células luteínicas grandes de vacas prenhes com seneciose crônica / Large luteal cell megalocytosis in pregnant cows with chronic seneciosis

Diversas espécies de Senecio estão amplamente difundidas nas pastagens de propriedades rurais do Sul do Brasil. Criadores dessa região relatam quedas nos índices reprodutivos dos rebanhos bovinos, muitas vezes de causas não determinadas. Várias plantas tóxicas são capazes de causar alterações reprodutivas diretas e indiretas em bovinos em diversos países, incluindo o Brasil, no entanto seus mecanismos patogenéticos ainda são pouco compreendidos. O objetivo desse trabalho é descrever lesões ovarianas em vacas com seneciose crônica proveniente de propriedades rurais da mesorregião Sudoeste Rio-grandense. Foram estudados 21 casos positivos de seneciose crônica diagnosticados entre 2011 e 2014. O estudo revelou que a seneciose crônica é a principal causa de morte de bovinos adultos na região. Quatro vacas prenhes apresentaram lesões hepáticas clássicas da intoxicação por Senecio spp. Essas vacas tiveram seus ovários avaliados histologicamente e células luteínicas grandes (CLG) desses ovários apresentavam megalocitose e pseudoinclusões nucleares. Algumas CLG apresentaram núcleos com até 23,69μm de diâmetro e o aumento no tamanho desses núcleos foi significativamente maior que os de vacas controle. Conclui-se que a intoxicação por Senecio spp. causa alterações ovarianas em vacas e é possível que a intoxicação cause perdas reprodutivas nos rebanhos bovinas da região...

Several species of Senecio are widely distributed on pasture lands in Southern Brazil. Farmers from this region are known to complain about declines in reproductive rates in cattl from undetermined causes. Several poisonous plants can cause direct and indirect reproductive disorders in cattle in several countries, including Brazil. However, their pathogenetic mechanisms are still poorly understood. The aim of this study is to describe ovarian lesions in cows with chronic seneciosis, from farms located in the Southwest Mesoregion of Rio Grande do Sul, a southern state in Brazil. Twenty-one cases of bovine chronic seneciosis diagnosed between 2011 and 2014 were analyzed. The study showed that chronic seneciosis is the major cause of death in adult cattle in the region. Four pregnant cows showing classical necropsy large luteal cells (LLG) from the ovaries of these four cows had marked megalocytosis and nuclear pseudo-inclusions. Some LLG showed nuclei with up to 23.69μm in diameter and the increase in size of these nuclei was significantly greater than measured those of control cows. It is concluded that the ingestion Senecio spp. induces ovarian changes in cows and the intoxication should be considered as a possible cause of reproductive failure in cattle herds from this region...

Hepatic Sinusoidal Obstruction Syndrome Caused by Herbal Medicine: CT and MRI Features

OBJECTIVE: To describe the CT and MRI features of hepatic sinusoidal obstruction syndrome (HSOS) caused by herbal medicine Gynura segetum. MATERIALS AND METHODS: The CT and MRI features of 16 consecutive Gynura segetum induced HSOS cases (12 men, 4 women) were analyzed. Eight patients had CT; three patients had MRI, and the remaining five patients had both CT and MRI examinations. Based on their clinical presentations and outcomes, the patients were classified into three categories: mild, moderate, and severe. The severity of the disease was also evaluated radiologically based on the abnormal hepatic patchy enhancement in post-contrast CT or MRI images. RESULTS: Ascites, patchy liver enhancement, and main right hepatic vein narrowing or occlusion were present in all 16 cases. Hepatomegaly and gallbladder wall thickening were present in 14 cases (87.5%, 14/16). Periportal high intensity on T2-weighted images was present in 6 cases (75%, 6/8). Normal liver parenchymal enhancement surrounding the main hepatic vein forming a clover-like sign was observed in 4 cases (25%, 4/16). The extent of patchy liver enhancement was statistically associated with clinical severity classification (kappa = 0.565). CONCLUSION: Ascites, patchy liver enhancement, and the main hepatic veins narrowing were the most frequent signs of herbal medicine induced HSOS. The grade of abnormal patchy liver enhancement was associated with the clinical severity.

Gulran disease: an outbreak in Afghanistan

On 2 April 2008, the Ministry of Public Health [MOPH], Afghanistan reported an outbreak in Western Afghanistan, in the Gulran district of Herat Province. The outbreak presented as hepatic venoocclusive disease [VOD]. This outbreak started in November 2007. As of April 2008 a total of 175 cases, including 13 deaths were reported from more than 17 villages. The disease is believed to be caused by exposure to pyrrolizidine alkaloids [PAs]. Preliminary results of charmac samples from Gulran tested in the National Institute for Public Health and the Environment [RIVM] Laboratory, The Netherlands show high levels of PAs, mostly heliotrine and lasiocarpine. On 3 May 2008, WHO and MOPH visited the Gulran district headquarters of Qarabagh and the village of Zergy, the first village to report Gulran disease

Doença veno-oclusiva hepática: relato de um caso / Hepatic veno-occlusive disease: report of a case

Objetivo: Alertar os pediatras para uma doença decorrente do uso de ervas consideradas inócuas. Métodos: Descriçä de um caso de hipertensäo porta de início súbito, secundária à Doença Veno-Oclusiva Hepátiaca em um paciente de 2 anos e 5 meses, proveniente de Cruz Alta, RS, após uso crônico de chás de "maria-mole" (Senecio brasiliensis), que contém alcalóides pirrolizidínicos, sabidamente hepatotóxicos. após tratamento adequado, apresentou recuperaçäo clínica e laboratorial completa e hoje encontra-se assintomático. Conclusöes: A prevençäo dessa doença depende da sua divulgaçäo entre médicos e populaçäo em geral, bem como do conhecimento dos efeitos tóxicos de muitos chás.

Enfermedad hepática veno-oclusiva asociada a la ingestión de humanrripa (senecio tephrosioides) / Hepatic veno-oclusive disease associated to ingetion of huamanrripa (senecio tephrosioides)

Se reporta un caso de enfermedad veno-oclusiva del hígado (EHVO) en una mujer de 38 años de edad que había consumido ocasionalmente "huamanrripa" (Senecio tephrosioides) durante algunos años como antitusígeno. Fue hospitalizada por presentar dolor abdominal difuso, ictericia y anasarca durante 10 semanas. El estudio histológico de la biopsia hepática mostró marcada congestión a predominio centrolobulillar, focos de necrosis y en algunas áreas, inversión de la arquitectura del lobulillo hepático. En los siguientes 13 meses ha sido hospitalizada en 4 ocasiones por complicaciones de hipertensión portal. Este es el primer caso reportado de enfermedad hepática veno-oclusiva asociada a la ingesta de S. tephrosioides. Es muy probable que esta planta usada en la medicina tradicional peruana contenga alcaloides pirrolizidina, sustancias hepato- y nefrotóxicas que estan presentes en otras especies del género Senecio. Debido a la popularidad actual de las medicinas alternativas se espera un aumento en la incidencia de EHVO

Action of the pyrrolizidine alkaloid integerrimine in inducing meiotic chromosome aberrations in male mice

A fase S (pré-leptoteno) da meiose masculina de camundongos C3H/HeJ e C57BL/6, foi exposta às doses 6,25; 12,50; 25 e 50 mg/kg de peso corpóreo do alcalóide pirrolizidínico integerrimina. Näo observamos efeitos sobre as aberraçöes cromossômicas, estruturais e numéricas, analisadas em diacinese/metáfase I

Effects of integerrimine on the implantation and intrauterine development of mice

Fêmeas gestantes de camundongos foram tratadas com o alcalóide pirrolizidínico integerrimina e foram analisadas quanto à perda pré e pós-implantaçäo e induçäo de malformaçöes congênitas. As fêmeas foram tratadas nos estágios de 0-10 horas, 58-64 horas, 5§ e 8§ dias gestacionais, com as doses de 0;25;37,5 e 50 mg/kg de peso corpóreo. Os resultados mostram que 1) o estágio 0-10 horas é o mais sensível para perdas pré-implantaçäo na linhagem C57BL/6; 2) os estágios de 3§ e 8§. dias säo mais sensíveis para perdas pós-implantaçäo para C57BL/6; 3) a integerrimina induz malformaçöes em fetos da linhagem C57BL/6 cujas mäes foram tratadas no 3§ dia gestacional. A linhagem C3H/HeJ näo apresentou malformaçöes embrionárias nos estágios e doses analisadas