Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS be...Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.展开更多
Pyrrolizidine alkaloids are a class of hepatotoxic and tumorigenic compounds detected in Chinese herbal plants, contaminated foods, and dietary supplements. In this review, the sources, toxicity, genotoxicity, tumorig...Pyrrolizidine alkaloids are a class of hepatotoxic and tumorigenic compounds detected in Chinese herbal plants, contaminated foods, and dietary supplements. In this review, the sources, toxicity, genotoxicity, tumorigenicity, and the metabolic pathways, particular the activation pathways leading to hepatotoxicity and tumorigenicity, of pyrrolizidine alkaloids are briefly discussed, with a focus on the most recent important findings concerning the genotoxic mechanism by which riddelliine liver tumors. This mechanism involves the formation of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and may be general to most carcinogenic pyrrolizidine alkaloids.展开更多
Natural products have attracted the interest of the scientific community due to their importance and application.Alexine is a naturally polyhydroxylated pyrrolizidine alkaloid that is broadly found in plant sources an...Natural products have attracted the interest of the scientific community due to their importance and application.Alexine is a naturally polyhydroxylated pyrrolizidine alkaloid that is broadly found in plant sources and isolated from Alexa leiopetala.The biological properties such as glycosidase inhibitors,anti-virus,and anti-HIV activities,makes it interesting target for synthetical studies.This review reports different approaches and methodologies to the synthesis of alexine,and its stereoisomers as the target compounds in numerous studies.展开更多
BACKGROUND Treatments for hepatic sinusoidal obstruction syndrome(HSOS)are limited.AIM To evaluate transjugular intrahepatic portosystemic shunting(TIPS)as a treatment for pyrrolidine alkaloid-related HSOS(PA-HSOS).ME...BACKGROUND Treatments for hepatic sinusoidal obstruction syndrome(HSOS)are limited.AIM To evaluate transjugular intrahepatic portosystemic shunting(TIPS)as a treatment for pyrrolidine alkaloid-related HSOS(PA-HSOS).METHODS This retrospective analysis included patients with PA-HSOS admitted to the First Affiliated Hospital of the University of Science and Technology of China(June 2015 to January 2019).Baseline clinical characteristics and follow-up data were extracted from the medical records.All patients included in this study experienced failure of initial therapy.Patients were divided into the TIPS and conservative treatment groups according to the therapy they received.Liver function,maximal ascites depth,imaging characteristics,pathology findings,and survival were compared between groups.RESULTS The TIPS group included 37 patients(28 males),and the conservative treatment group included 17 patients(11 males).Baseline characteristics were similar between groups.There were two deaths in the TIPS group and seven deaths in the conservative treatment group during follow-up(3-48 mo).The 3-,6-,12-and 24-mo survival rates were 94.6%,94.6%,94.6%and 94.6%,respectively,in the TIPS group and 70.6%,57.8%,57.8%and 57.8%,respectively,in the conservative treatment group.Kaplan-Meier analysis revealed significantly longer survival for the TIPS group than for the conservative treatment group(P=0.001).Compared with the pre-treatment value,maximal ascites depth was significantly lower at 1 wk,2 wk,1 mo,and 3 mo for the TIPS group(all P<0.05)but not in the conservative treatment group.Contrast-enhanced computed tomography demonstrated the disappearance of patchy liver enhancement after TIPS.Pathology showed that liver congestion and hepatocyte swelling improved with time after TIPS placement.CONCLUSION TIPS may achieve better outcomes than conventional symptomatic treatment in patients with PA-HSOS.展开更多
基金Supported by National Natural Science Foundation of China,No.81570555 and No.81770582
文摘Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.
基金This article is not an official U.S. Food and Drug Administration guidance or policy statement. No official support or endorsement by the U.S. Food and DrugAdministration is intended or should be inferred.
文摘Pyrrolizidine alkaloids are a class of hepatotoxic and tumorigenic compounds detected in Chinese herbal plants, contaminated foods, and dietary supplements. In this review, the sources, toxicity, genotoxicity, tumorigenicity, and the metabolic pathways, particular the activation pathways leading to hepatotoxicity and tumorigenicity, of pyrrolizidine alkaloids are briefly discussed, with a focus on the most recent important findings concerning the genotoxic mechanism by which riddelliine liver tumors. This mechanism involves the formation of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and may be general to most carcinogenic pyrrolizidine alkaloids.
文摘Natural products have attracted the interest of the scientific community due to their importance and application.Alexine is a naturally polyhydroxylated pyrrolizidine alkaloid that is broadly found in plant sources and isolated from Alexa leiopetala.The biological properties such as glycosidase inhibitors,anti-virus,and anti-HIV activities,makes it interesting target for synthetical studies.This review reports different approaches and methodologies to the synthesis of alexine,and its stereoisomers as the target compounds in numerous studies.
基金Supported by China Hepatitis Prevention and Treatment Foundation Scientific Research Subject,No. TQGB20180247Anhui Province Natural Science Foundation Projects,No.1808085MH254
文摘BACKGROUND Treatments for hepatic sinusoidal obstruction syndrome(HSOS)are limited.AIM To evaluate transjugular intrahepatic portosystemic shunting(TIPS)as a treatment for pyrrolidine alkaloid-related HSOS(PA-HSOS).METHODS This retrospective analysis included patients with PA-HSOS admitted to the First Affiliated Hospital of the University of Science and Technology of China(June 2015 to January 2019).Baseline clinical characteristics and follow-up data were extracted from the medical records.All patients included in this study experienced failure of initial therapy.Patients were divided into the TIPS and conservative treatment groups according to the therapy they received.Liver function,maximal ascites depth,imaging characteristics,pathology findings,and survival were compared between groups.RESULTS The TIPS group included 37 patients(28 males),and the conservative treatment group included 17 patients(11 males).Baseline characteristics were similar between groups.There were two deaths in the TIPS group and seven deaths in the conservative treatment group during follow-up(3-48 mo).The 3-,6-,12-and 24-mo survival rates were 94.6%,94.6%,94.6%and 94.6%,respectively,in the TIPS group and 70.6%,57.8%,57.8%and 57.8%,respectively,in the conservative treatment group.Kaplan-Meier analysis revealed significantly longer survival for the TIPS group than for the conservative treatment group(P=0.001).Compared with the pre-treatment value,maximal ascites depth was significantly lower at 1 wk,2 wk,1 mo,and 3 mo for the TIPS group(all P<0.05)but not in the conservative treatment group.Contrast-enhanced computed tomography demonstrated the disappearance of patchy liver enhancement after TIPS.Pathology showed that liver congestion and hepatocyte swelling improved with time after TIPS placement.CONCLUSION TIPS may achieve better outcomes than conventional symptomatic treatment in patients with PA-HSOS.
