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.
Subject(s)
Drugs, Chinese Herbal , Hepatic Veno-Occlusive Disease , Animals , Apoptosis , Autophagy , Hepatic Veno-Occlusive Disease/chemically induced , Hepatic Veno-Occlusive Disease/pathology , Liver/pathology , MiceABSTRACT
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.
Subject(s)
Animals , Mice , Hepatic Veno-Occlusive Disease/chemically induced , Hepatic Veno-Occlusive Disease/pathology , Drugs, Chinese Herbal , Autophagy , Apoptosis , Liver/pathologyABSTRACT
BACKGROUND: Chemotherapy-associated liver injury (CALI) is a matter of concern for hepatobiliary surgeons as it can entail postoperative liver failure after an extensive hepatectomy. Recent studies have taken special interest in liver function parameters which can correlate with CALI to decrease this adverse event. Therefore, the current study investigates the usefulness of splenic volume as a biomarker of CALI through a portal hypertension mechanism, in patients with colorectal liver metastases (CRLM). STUDY DESIGN: We carried out a study in patients with CRLM operated on between 2009 and 2014 in our center. All samples of healthy liver were graded for non-alcoholic fatty liver disease (NAFLD) and sinusoidal obstructive syndrome. Computarized tomography scans for spleen volumetry were analyzed for each patient at CRLM diagnosis, after neoadjuvant chemotherapy, 1 and 6 months after resection. RESULTS: A group of 65 consecutive patients with CRLM of large bowel adenocarcinoma submitted to liver resection were included. Patients receiving neoadjuvant chemotherapy had a greater spleen volume increase than those who did not receive treatment (p = 0.053), finding a statistically significant spleen growth in patients with NAFLD (p = 0.036). There was no correlation between spleen enlargement and postoperative complications or average stay. However, survival was decreased in patients with spleen growth and CALI. CONCLUSIONS: Patients who receive neoadjuvant chemotherapy for liver metastasis surgery have a greater splenic volume increase, which correlates with NAFLD and a lower survival.
Subject(s)
Adenocarcinoma/therapy , Antineoplastic Agents/adverse effects , Chemical and Drug Induced Liver Injury/pathology , Colorectal Neoplasms/pathology , Hepatectomy , Hepatic Veno-Occlusive Disease/pathology , Liver Neoplasms/therapy , Non-alcoholic Fatty Liver Disease/pathology , Spleen/diagnostic imaging , Adenocarcinoma/secondary , Antineoplastic Agents/therapeutic use , Chemical and Drug Induced Liver Injury/etiology , Fatty Liver/chemically induced , Fatty Liver/pathology , Hepatic Veno-Occlusive Disease/chemically induced , Humans , Liver Neoplasms/secondary , Metastasectomy , Neoadjuvant Therapy , Non-alcoholic Fatty Liver Disease/chemically induced , Organ Size , Oxaliplatin/adverse effects , Oxaliplatin/therapeutic use , Postoperative Complications , Spleen/pathology , Survival Rate , Tomography, X-Ray ComputedSubject(s)
Humans , Infant , Antineoplastic Agents/adverse effects , Hepatic Veno-Occlusive Disease/chemically induced , Hepatic Veno-Occlusive Disease/diagnosis , Hepatic Veno-Occlusive Disease/etiology , Retroperitoneal Neoplasms/drug therapy , Rhabdomyosarcoma/drug therapy , Diagnosis, Differential , Hepatomegaly , Jaundice , Lung Neoplasms/secondary , Urinary RetentionABSTRACT
Veno-occlusive liver disease is a well-known clinico-pathological entity. Etiology is varied but the most frequent cause is toxicity. Pirrolizadimic alkaloids, which are found in a large number of vegetables and which are used as therapy, have been identified as the direct origin of this process. We report a 23-year-old woman who presented with abdominal distension. Ascites was recorded semiologically. Laboratory studies and liver biopsy were performed. Histopathology revealed alterations characteristic of veno-occlusive disease and hepatic hemodynamic studies confirmed the diagnosis. Due to chronic constipation, the patient had been taking commercial preparations of herbal infusions which contained Senecio vulgaris. Outcome was favorable and periodic clinical check-ups have been normal to date. The presentation of this case as acute veno-occlusive disease due to pirrolizidinic alkaloids as well as the clinical remission of the effects in the liver are emphasized.
Subject(s)
Beverages/poisoning , Hepatic Veno-Occlusive Disease/chemically induced , Senecio/poisoning , Adult , Female , HumansABSTRACT
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.
Subject(s)
Humans , Male , Child, Preschool , Hepatic Veno-Occlusive Disease/chemically induced , Hepatic Veno-Occlusive Disease/complications , Hypertension, Portal/etiology , Pyrrolizidine Alkaloids/adverse effects , Ascites/etiology , Hepatomegaly/etiology , Venules/pathologyABSTRACT
We report a 30 years old male, recipient of a kidney allograft and treated with azathioprine, who eighteen days after transplantation had a clinically asymptomatic elevation of total bilirubin and alkaline phosphatases. Nineteen months later, he presented with mild ascites, with a total bilirubin of 3.5 mg/dl, alkaline phosphatases of 308 U/L (normal < 170 U/L) and a prothrombin time at 55% of control. A liver biopsy showed sinusoidal and perivenular fibrosis without inflammation, compatible with chronic venous obstruction. Hepatic veno-occlusive disease is an infrequent complication of azathioprine use.
Subject(s)
Azathioprine/adverse effects , Hepatic Veno-Occlusive Disease/chemically induced , Immunosuppressive Agents/adverse effects , Kidney Failure, Chronic/surgery , Kidney Transplantation , Adult , Azathioprine/therapeutic use , Hepatic Veno-Occlusive Disease/diagnosis , Humans , Immunosuppressive Agents/therapeutic use , MaleABSTRACT
We report a 30 years old male, recipient of a kidney allograft and treated with azathioprine, who 18 days after transplantation had a clinically asymptomatic elevation of total bilirrubin and alkaline phosphatases. Nineteen months later, he presented with mild ascites, with a total bilirrubin of 3.5 mg/dl, alkaline phosphatases of 308 U/L (normal <170 U/L) and a prothrombin time at 55 percent of control. A liver biopsy showed sinusoidal and perivenular fibrosis without inflammation, compatible with chronic venous obstruction. Hepatic veno-occlusive disease is an infrequent complication of azathioprine use
Subject(s)
Humans , Male , Adult , Azathioprine/adverse effects , Hepatic Veno-Occlusive Disease/chemically induced , Biopsy , Kidney Transplantation , Cyclophosphamide/administration & dosageABSTRACT
A case of hepatic veno-occlusive disease (HVOD) in a 38 year-old woman is reported. She had occasionally consumed "Huamanrripa" (Senecio tephrosioides) as a cough remedy for many years. She was hospitalized because she had presented abdominal pain, jaundice and anasarca during 10 weeks. The histological studies of hepatic biopsy showed pronounced congestion to centrilobulillar predominance, focus of necrosis and a reversed lobulation pattern in some areas. In the next 13 months she was hospitalized four times due to complications of portal hypertension. This is the first reported case of HVOD associated with S tephrosioides ingestion. It is very probable that this plant used in peruvian traditional medicine contains pyrrolizidine alkaloids, hepatic and nephrotoxic substances that are present in other species of Senecio genus. Due to present popularity of alternative medicine, an increment in HVOD incidence is expected.
Subject(s)
Beverages/adverse effects , Hepatic Veno-Occlusive Disease/chemically induced , Plants, Medicinal , Plants, Toxic , Pyrrolizidine Alkaloids/adverse effects , Senecio , Adult , Bolivia , Female , Humans , PeruABSTRACT
Os autores apresentam um caso de doença venoclusiva hepática em um paciente de 1 mês e 28 anos de idade, possivelmente causada por ingesta de chás contaminados por alcalóides da pirrolizidina (SENECIO). Outras causas potenciais foram afastadas. O diagnóstico foi confirmado por exame anátomo-patológico, com retirada de fragmento por biópsia hepática. Säo enfatizados aspectos epidemiológicos e as possíveis razöes do número reduzido de casos relatados de doença venoclusiva hepática em nosso estado