Pyrrolizidine alkaloids(PAs) are widely dispersed in the plants,and approximately 120 PAs could induce liver toxicity.Compositae,Boraginaceae,Leguminosae and several families in the plants contain PAs.In recent years,there are many HPAs-induced liver injuries caused by the use of Gynura segetum(Lour.) Merr in China and these events caused the extensive concern.By reviewing the relevant literatures,the pathogenesis,mechanism,diagnosis and treatment,risk factor as well as risk management was studied,in order to provide reference for clinical application and risk management of the HPAs-containing herbs such as Gynura segetum(Lour.) Merr.
DELEVE LD,MCCUSKEY RS,WANGX,et al.Charac-terization of a reproducible rat model of hepatic veno-occlusive disease[J].Hepatology,1999,29(6):1779-1791.
Lack of a reproducible animal model has hampered progress in understanding hepatic veno-occlusive disease (HVOD). This article characterizes a reproducible model of HVOD. Rats gavaged with monocrotaline, 160 mg/kg, were killed between days 1 and 10. Sections were evaluated by light microscopy with a standardized scoring system, by immunoperoxidase staining with ED-1 (monocytes, macrophages) and ED-2 (Kupffer cells) antibodies, and by transmission (TEM) and scanning electron microscopy (SEM). On days 1 and 2, the earliest manifestations were progressive injury to the sinusoidal wall with loss of sinusoidal lining cells, sinusoidal hemorrhage, and mild damage to central vein (CV) endothelium. On days 3 through 5 ("early HVOD"), there was centrilobular coagulative necrosis, severe injury to sinusoids, severe sinusoidal hemorrhage, and severe CV endothelial damage; inflammation with ED-1-positive cells was most marked on these days. Days 6 and 7 ("late HVOD") were characterized by subendothelial and advential fibrosis of CVs, damage of the CV endothelium with subendothelial hemorrhage, and some restoration of the sinusoidal wall. Between days 8 and 10, sections showed interindividual variation ranging from mild, residual fibrosis to severe, late HVOD. From days 1 through 10, ED-2-positive cells were decreased in number, and the number of ED-1-positive cells was increased. Sinusoidal damage is the earliest change in HVOD. Coagulative necrosis follows sinusoidal injury and resolves with improvement in sinusoidal endothelial cell (SEC) morphology. Moderate-to-severe CV fibrosis occurs after reappearance of sinusoidal lining cells and resolution of hepatocyte necrosis. The inflammatory response within the lobule and CVs is a result of recruitment of monocytes, whereas Kupffer cells are decreased in number.
ROEDERE,WIEDENFELDH,EDGAR JA.Pyrrolizidine alkaloids in medicinal plants from North America[J].Pharmazie,2015,70(6):357-367.
Pyrrolizidine alkaloids (PAs) are mutagenic, carcinogenic, pneumotoxic, teratogenic and fetotoxic. Plants containing PAs commonly poison livestock in many countries, including the USA and Canada. In some regions of the world PA-producing plants sometimes grow in grain crops and items of food made with PA contaminated grain, such as bread baked using contaminated flour, have been, and continue to be, responsible for large incidents of acute, often fatal human poisoning. Herbal medicines and food supplements containing PAs are also recognized as a significant cause of human poisoning and it is desirable that such medications are identified and subjected to strict regulation. In this review we consider the PAs known to be, or likely to be, present in both the traditionally used medicinal plants of North America and also medicinal plants that have been introduced from other countries and are being recommended and used as phytopharmaceuticals in the USA and Canada.
DUSEMUNDB,RIETJENS I M C M,CARTUS A,et al.Plant-derived contaminants in food:occurrence,effects and risk assessment[J].Bundesgesundheitsblatt Gesundheits-forschung Gesundheitsschutz,2017,60(7):728-736.
Among the various contaminants, the group of natural plant-derived substances in the modern food chain has been generating increasing concern in recent years. The adverse effects encountered may be diverse and pose risks of acute, subchronic or chronic toxicity. The underlying mechanisms of toxicity may be thresholded or be based on interactions with DNA, as for genotoxic carcinogens, for which the existence of a threshold cannot be assumed. This article gives an overview of the major plant-derived contaminants of present concern in the modern food chain and describes their mode of action and adverse effects.
BODID,RONCZKAS,GOTTSCHALKC,et al.Determina-tion of pyrrolizidine alkaloids in tea,herbal drugs and honey[J].Food Addit Contam Part A,2014,31(11):1886-1895.
Honey was previously considered to be one of the main food sources of human pyrrolizidine alkaloid (PA) exposure in Europe. However, comprehensive analyses of honey and tea sampled in the Berlin retail market revealed unexpected high PA amounts in teas. This study comprised the analysis of 87 honey as well as 274 tea samples including black, green, rooibos, melissa, peppermint, chamomile, fennel, nettle, and mixed herbal tea or fruit tea. Total PA concentrations in tea ranged from < LOD to 5647 0008g kg0908081, while a mean value of about 10 0008g kg0908081 was found in honey samples. Additionally, herbal drugs were investigated to identify the source of PA in teas. Results suggest that PA in tea samples are most likely a contamination caused by co-harvesting of PA-producing plants. In some cases such as fennel, anise or caraway, it cannot be excluded that these plants are able to produce PA themselves.
NEUMAN MG,COHEN LB,STEENKAMPV.Pyrrolizi-dine alkaloids enhance alcohol-induced hepatocytotoxicity in vitro in normal human hepatocytes[J].Eur Rev Med Pharmacol Sci,2017,21(S1):53-68.
Pyrrolizidine alkaloids(PAs) are widely distributed in many plants including medicinal herbs. The hepatotoxicity of PAs has been known academically for a long time, however, their reproductive toxicity, mutagenesis and carcinogenicity have been less researched. This article is an overview of the clinical and experimental reports of the reproductive toxicity, mutagenesis and carcinogenicity of PAs, the effective factors and generating mechanism of the toxicity.
CHAUVINP,DILLON JC,MORENA.An outbreak of Heliotrope food poisoning,Tajikistan,November 1992-March 1993[J].Sante,1994,4(4):263-268.
The seeds and roots of Heliotropium lasocarpium, contain a pyrrolizidine alkaloid which causes toxic liver injury and veno-occlusive disease (VOD), characterised by an occlusive lesion of the centrolobular veins of the liver, when consumed by humans. The Farkhar region of Southern Tadjikistan, was blockaded from May to November 1992. This led to a famine and a delay of two months in the wheat harvest. Heliotropium lasocarpium had time to grow in the fields and their seeds were therefore collected with the wheat. The contaminated wheat was distributed to the population, who milled it and made bread. The first case of liver toxicity was six weeks after the first consumption of the contaminated bread. By March 1993, 3,906 cases had been recorded (attack rate = 4%). The attack rate were 0.4%, 5.4%, 4.0%, 2.8% and 1.5% for the less than 1 year, 1-14 years, 15-30 years, 31-50 years and over 50 years age groups respectively. The overall case fatality ratio (CFR) was 1.3% and increased with age from 0 to 5.9% in the same age groups. Two of the ten collective farms represented 83.3% of the cases attack rate of 16.9% and 23.6%. Four stages of illness were defined. Stage I corresponds to abdominal pain, nausea or vomiting, and asthenia. All stage I patients (55.5%) recovered rapidly. Stage II is an association of Stage I and hepatomegalia (29.9%). Stage III includes ascites in addition to these symptoms (13.7%) and stage IV alteration of consciousness (0.9%). The last case was reported on March 4th 1993.(ABSTRACT TRUNCATED AT 250 WORDS)
MCDONALD GB,HINDS MS,FISHER LD,et al.Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation:a cohort study of 355 patients[J].Anna Int Med,1993,118(4):255-267.
, 宋海波
