Database : MEDLINE
Search on : Pyrrolizidine and Alkaloids [Words]
References found : 1931 [refine]
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  1 / 1931 MEDLINE  
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[PMID]: 29524571
[Au] Autor:Dusemund B; Nowak N; Sommerfeld C; Lindtner O; Schäfer B; Lampen A
[Ad] Address:Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 10, 10589 Berlin, Germany. Electronic address: Birgit.Dusemund@bfr.bund.de.
[Ti] Title:Risk assessment of pyrrolizidine alkaloids in food of plant and animal origin.
[So] Source:Food Chem Toxicol;, 2018 Mar 07.
[Is] ISSN:1873-6351
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Acute liver toxicity, specifically in the form of hepatic veno-occlusive disease (HVOD), is known from reports on human poisonings following ingestions of 1,2-unsaturated pyrrolizidine alkaloids (PAs) containing herbs. Recently PA exposure via common foods contaminated via PA-producing plants raised concern, especially regarding the potential of genotoxicity and carcinogenicity. The health risks related to the estimated exposures to PAs from food were assessed. With respect to common foods, herbal teas and teas are the main sources through which consumers can be exposed to PAs. For high long-term consumption of these foods a possible health concern has been revealed in the assessment of chronic risks referring to a BMDL of 237 µg/kg bw per day recently established by EFSA based on model averaging for data on riddelliine. However, acute health damage from acute or short-term intake of PAs via common food is considered to be unlikely. Food supplements on the basis of PA-producing plants may significantly contribute to PA exposures and their intake is associated with risks of acute and chronic toxicity. However, no health risks have to be expected from the consumption of food supplements based on oil-based preparations of PA-producing plants, which were described to be free of PAs.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  2 / 1931 MEDLINE  
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[PMID]: 29353003
[Au] Autor:Qiu S; Zhang H; Fei Q; Zhu F; Wang J; Jia X; Chen B
[Ad] Address:Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Shi Zi Street No. 100, Hongshan Road, Jiangsu, Nanjing 210028, China; Key Laboratory of Chinese Medicine Delivery System of State Administration of Traditional Chinese Medicine, Jiangs
[Ti] Title:Urine and plasma metabolomics study on potential hepatoxic biomarkers identification in rats induced by Gynura segetum.
[So] Source:J Ethnopharmacol;216:37-46, 2018 Apr 24.
[Is] ISSN:1872-7573
[Cp] Country of publication:Ireland
[La] Language:eng
[Ab] Abstract:ETHNOPHARMACOLOGICAL RELEVANCE: Gynura segetum (GS) is an herbal medicine containing Pyrrolizidine Alkaloids (PAs) that causes hepatic sinusoidal obstruction syndrome (HSOS). AIM OF THE STUDY: To discover potential biomarkers and metabolic mechanisms involved in the hepatotoxicity induced by GS. METHODS: SD rats were randomly divided into 4 groups including Saline, the decoction of GS high, medium and low dosage at dosages of 3.75g • kg , 7.5g • kg and 15g • kg . A metabolomics approach using Ultraperformance Liquid Chromatography -Quadrupole-Time-of-Flight / Mass Spectrometry (UPLC-Q-TOF/MS) was developed to perform the plasma and urinary metabolic profiling analysis, and identified differential metabolites by comparing the saline control group and decoction of GS groups. RESULTS: The herbal was presented dosage-dependent led to ingravescence of hepatotoxicity after the rats were consecutively given with the decoction of GS at varied dosages. A total of 18 differential metabolites of decoction of GS-induced hepatotoxicity were identified, while 10 of them including arginine, proline, glutamate, creatine, valine, linoleic acid, arachidonic acid, sphinganine, phytosphingosine, and citric acid could be discovered in urine and plasma, and primarily involved in Amino acid metabolism, Lipids metabolism and Energy metabolism. CONCLUSIONS: The results suggested that the differential metabolites of arginine, creatine, valine, glutamine and citric acid were verified as potential markers of GS-induced hepatotoxicity via the regulation of multiple metabolic pathways primarily involving in Amino acids metabolism and Energy metabolism.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:In-Process

  3 / 1931 MEDLINE  
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[PMID]: 29458164
[Au] Autor:Waizenegger J; Braeuning A; Templin M; Lampen A; Hessel-Pras S
[Ad] Address:German Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Straße 8-10, 10589 Berlin, Germany.
[Ti] Title:Structure-dependent induction of apoptosis by hepatotoxic pyrrolizidine alkaloids in the human hepatoma cell line HepaRG: Single versus repeated exposure.
[So] Source:Food Chem Toxicol;114:215-226, 2018 Feb 16.
[Is] ISSN:1873-6351
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Pyrrolizidine alkaloids (PA) are secondary plant compounds. PA intoxication in humans causes severe acute and chronic hepatotoxicity. However, the molecular mechanisms of PA hepatotoxicity in humans are not well understood yet. Therefore, we investigated cell death parameters in human HepaRG cells following either single (24 h) or repeated dose treatment (14 d) with structurally different PA of the retronecine (echimidine, senecionine), heliotridine (heliotrine), and otonecine type (senkirkine). After 24 h of exposure only retronecine-type PA were cytotoxic in HepaRG cells and induced apoptosis indicated by a loss of membrane asymmetry, disruption of the mitochondrial membrane potential, and increased pro-caspase and PARP cleavage. In contrast, after 14 d all four PA exerted the aforementioned effects. Furthermore, the apoptotic events caspase 3, 8 and 9 activation as well as nuclear condensation and DNA fragmentation were only detected for the retronecine-type PA after single exposure (6 h). Overall, our studies revealed a time- and structure-dependent apoptosis after PA exposure, suggesting that retronecine-type PA seem to be more potent apoptosis inducers than heliotridine- or otonecine-type PA. Furthermore, our results suggest that PA-induced apoptosis in HepaRG cells occur most probably by involving both, the extrinsic death receptor pathway as well as the intrinsic mitochondrial pathway.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher

  4 / 1931 MEDLINE  
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[PMID]: 29392532
[Au] Autor:Hill EM; Robinson LA; Abdul-Sada A; Vanbergen AJ; Hodge A; Hartley SE
[Ad] Address:School of Life Sciences, University of Sussex, Brighton, BN1 9QG, UK.
[Ti] Title:Arbuscular Mycorrhizal Fungi and Plant Chemical Defence: Effects of Colonisation on Aboveground and Belowground Metabolomes.
[So] Source:J Chem Ecol;44(2):198-208, 2018 Feb.
[Is] ISSN:1573-1561
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Arbuscular mycorrhizal fungal (AMF) colonisation of plant roots is one of the most ancient and widespread interactions in ecology, yet the systemic consequences for plant secondary chemistry remain unclear. We performed the first metabolomic investigation into the impact of AMF colonisation by Rhizophagus irregularis on the chemical defences, spanning above- and below-ground tissues, in its host-plant ragwort (Senecio jacobaea). We used a non-targeted metabolomics approach to profile, and where possible identify, compounds induced by AMF colonisation in both roots and shoots. Metabolomics analyses revealed that 33 compounds were significantly increased in the root tissue of AMF colonised plants, including seven blumenols, plant-derived compounds known to be associated with AMF colonisation. One of these was a novel structure conjugated with a malonyl-sugar and uronic acid moiety, hitherto an unreported combination. Such structural modifications of blumenols could be significant for their previously reported functional roles associated with the establishment and maintenance of AM colonisation. Pyrrolizidine alkaloids (PAs), key anti-herbivore defence compounds in ragwort, dominated the metabolomic profiles of root and shoot extracts. Analyses of the metabolomic profiles revealed an increase in four PAs in roots (but not shoots) of AMF colonised plants, with the potential to protect colonised plants from below-ground organisms.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Process
[do] DOI:10.1007/s10886-017-0921-1

  5 / 1931 MEDLINE  
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[PMID]: 29485280
[Au] Autor:Chung SWC; Lam CH
[Ad] Address:Food Research Laboratory , Centre for Food Safety, Food and Environmental Hygiene Department , 4/F Public Health Laboratory Centre, 382 Nam Cheong Street , Hong Kong.
[Ti] Title:Development of an Analytical Method for Analyzing Pyrrolizidine Alkaloids in Different Groups of Food by UPLC-MS/MS.
[So] Source:J Agric Food Chem;, 2018 Mar 05.
[Is] ISSN:1520-5118
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Suspected nontargeted pyrrolizidine alkaloids (PAs), without analytical reference standard, were observed and interfered with the determination of targeted PAs in complex food matrices, especially for spices samples. Selectivity and applicability of multiple reaction monitoring (MRM) transitions, multistage fragmentation (MS3), and MRM with differential ion mobility spectrometry (DMS) for eliminating false positive identifications were evaluated. Afterward, a selective and sensitive LC-MS/MS method for the determination of 15 PAs and 13 PA N-oxides in foodstuffs was developed. The sample preparation and cleanup are applicable to a wide range of foodstuffs, including cereal products, dairy products, meat, eggs, honey, tea infusion, and spices. Freezing-out of the raw extract and the water/acetonitrile washing steps in a solid phase extraction was found to efficiently remove complex matrices. The method was validated at 0.05 µg kg for general food and 0.5 µg kg for spices, with reference to the Eurachem Guide. The estimated limit of quantifications of different PAs was in the range of 0.010-0.087 µg kg for general food and 0.04-0.76 µg kg for spices. Isotopically labeled PAs were used as internal standards to correct the variation of PAs/PANs performance in different food commodities. Matrix effects observed in complex food matrices could be reduced by solvent dilution. Recoveries of PAs and PA N-oxides were all seen within 50-120%.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:Publisher
[do] DOI:10.1021/acs.jafc.7b06118

  6 / 1931 MEDLINE  
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[PMID]: 29454024
[Au] Autor:Forsch K; Schöning V; Disch L; Siewert B; Unger M; Drewe J
[Ad] Address:Max Zeller Söhne AG, CH-8590 Romanshorn, Switzerland.
[Ti] Title:Development of an in vitro screening method of acute cytotoxicity of the pyrrolizidine alkaloid lasiocarpine in human and rodent hepatic cell lines by increasing susceptibility.
[So] Source:J Ethnopharmacol;217:134-139, 2018 Feb 14.
[Is] ISSN:1872-7573
[Cp] Country of publication:Ireland
[La] Language:eng
[Ab] Abstract:ETHNOPHARMACOLOGICAL RELEVANCE: Pyrrolizidine alkaloids (PAs) are secondary plant ingredients formed in many plant species to protect against predators. PAs are generally considered acutely hepatotoxic, genotoxic and carcinogenic. Up to now, only few in vitro and in vivo investigations were performed to evaluate their relative toxic potential. AIM OF THE STUDY: The aim was to develop an in vitro screening method of their cytotoxicity. MATERIALS AND METHODS: Human and rodent hepatocyte cell lines (HepG2 and H-4-II-E) were used to assess cytotoxicity of the PA lasiocarpine. At concentrations of 25 µM up to even 2400 µM, no toxic effects in neither cell line was observed with standard cell culture media. Therefore, different approaches were investigated to enhance the susceptibility of cells to PA toxicity (using high-glucose or galactose-based media, induction of toxifying cytochromes, inhibition of metabolic carboxylesterases, and inhibition of glutathione-mediated detoxification). RESULTS: Galactose-based culture medium (11.1 mM) increased cell susceptibility in both cell-lines. Cytochrome P450-induction by rifampicin showed no effect. Inhibition of carboxylesterase-mediated PA detoxification by specific carboxylesterase 2 inhibitor loperamide (2.5 µM) enhanced lasiocarpine toxicity, whereas the unspecific carboxylesterase inhibitor bis(4-nitrophenyl)phosphate (BNPP, 100 µM)) had a weaker effect. Finally, the inhibition of glutathione-mediated detoxification by buthionine sulphoximine (BSO, 100 µM) strongly enhanced lasiocarpine toxicity in H-4-II-E cells in low and medium, but not in high concentrations. CONCLUSIONS: If no toxicity is observed under standard conditions, susceptibility enhancement by using galactose-based media, loperamide, and BSO may be useful to assess relative acute cytotoxicity of PAs in different cell lines.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180303
[Lr] Last revision date:180303
[St] Status:Publisher

  7 / 1931 MEDLINE  
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[PMID]: 29352068
[Au] Autor:Li X; Yang X; Xiang E; Luo J; Qiu S; Fang Y; Zhang L; Guo Y; Zheng J; Wang H
[Ad] Address:Department of Pharmacology, School of Basic Medical Science, Wuhan University, Wuhan (X.L., E.X., J.L., S.Q., Y.F., Y.G., H.W.); and Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan (Y.G., H.W.); Wuya College of Innovation, Shenyang Pharmaceutical Univer
[Ti] Title:Maternal-Fetal Disposition and Metabolism of Retrorsine in Pregnant Rats.
[So] Source:Drug Metab Dispos;46(4):422-428, 2018 Apr.
[Is] ISSN:1521-009X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Pyrrolizidine alkaloids (PAs) are extensively synthesized by plants, are commonly present in herbs and foodstuffs, and exhibit hepatotoxicity requiring metabolic activation by cytochrome P450 3A to form the electrophilic metabolites-pyrrolic esters. PAs also cause embryo toxicity, but the metabolic profiles of PAs in fetus and placenta have been far from clear. In this study, we determined the basal metabolic activation of retrorsine (RTS) in rat maternal liver, placenta, and fetal liver in vitro and examined the fetal toxicity and bioactivation of RTS in vivo. Detection of microsomal RTS metabolites in vitro showed that the basal metabolic activity of fetal liver and placenta to RTS was much weaker than that of maternal liver. In addition, a higher rate of pyrrolic ester formation was found in normal male fetal liver compared with that of female pups. In vivo exposure to RTS caused fetal growth retardation, as well as placental and fetal liver injury. Little difference in serum RTS was observed in dams and fetuses, but the content of pyrrole-protein adduction in the fetal liver was much lower than that in maternal liver, which was consistent with basal metabolic activity. Unexpectedly, compared with basal metabolism in fetal liver, exposure to RTS during middle and late pregnancy caused an opposite gender difference in RTS metabolism and CYP3A expression in the fetal liver. For the first time, our study showed that RTS can permeate the placenta barrier and entering fetal circulation, whereas the intrauterine pyrrolic metabolite was generated mainly by fetal liver but not transported from the maternal circulation. Induction of CYP3A by RTS was gender-dependent in the fetal liver, which was probably responsible for RTS-induced fetal hepatic injury, especially for female pups.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180227
[Lr] Last revision date:180227
[St] Status:In-Data-Review
[do] DOI:10.1124/dmd.117.079186

  8 / 1931 MEDLINE  
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[PMID]: 29479722
[Au] Autor:Livshultz T; Kaltenegger E; Straub SCK; Weitemier K; Hirsch E; Koval K; Mema L; Liston A
[Ad] Address:Department of Biodiversity, Earth, and Environmental Sciences, Academy of Natural Sciences of Drexel University, 1900 Benjamin Franklin Parkway, Philadelphia, PA, 19103, USA.
[Ti] Title:Evolution of pyrrolizidine alkaloid biosynthesis in Apocynaceae: revisiting the defence de-escalation hypothesis.
[So] Source:New Phytol;, 2018 Feb 26.
[Is] ISSN:1469-8137
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Plants produce specialized metabolites for their defence. However, specialist herbivores adapt to these compounds and use them for their own benefit. Plants attacked predominantly by specialists may be under selection to reduce or eliminate production of co-opted chemicals: the defence de-escalation hypothesis. We studied the evolution of pyrrolizidine alkaloids (PAs) in Apocynaceae, larval host plants for PA-adapted butterflies (Danainae, milkweed and clearwing butterflies), to test if the evolutionary pattern is consistent with de-escalation. We used the first PA biosynthesis specific enzyme (homospermidine synthase, HSS) as tool for reconstructing PA evolution. We found hss orthologues in diverse Apocynaceae species, not all of them known to produce PAs. The phylogenetic analysis showed a monophyletic origin of the putative hss sequences early in the evolution of one Apocynaceae lineage (the APSA clade). We found an hss pseudogene in Asclepias syriaca, a species known to produce cardiac glycosides but no PAs, and four losses of an HSS amino acid motif. APSA clade species are significantly more likely to be Danainae larval host plants than expected if all Apocynaceae species were equally likely to be exploited. Our findings are consistent with PA de-escalation as an adaptive response to specialist attack.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180226
[Lr] Last revision date:180226
[St] Status:Publisher
[do] DOI:10.1111/nph.15061

  9 / 1931 MEDLINE  
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[PMID]: 29377789
[Au] Autor:Gottschalk C; Ostertag J; Meyer K; Gehring K; Thyssen S; Gareis M
[Ad] Address:a Chair of Food Safety, Faculty of Veterinary Medicine , Ludwig-Maximilians-University Munich (LMU) , Oberschleissheim , Germany.
[Ti] Title:Influence of grass pellet production on pyrrolizidine alkaloids occurring in Senecio aquaticus-infested grassland.
[So] Source:Food Addit Contam Part A Chem Anal Control Expo Risk Assess;:1-10, 2018 Feb 23.
[Is] ISSN:1944-0057
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:1,2-Dehydro-pyrrolizidine alkaloids (PA) and their N-oxides (PANO) exhibit acute and chronic toxic effects on the liver and other organs and therefore are a hazard for animal and human health. In certain regions of Germany, an increasing spread of Senecio spp. (ragwort) on grassland and farmland areas has been observed during the last years leading to a PA/PANO-contamination of feed and food of animal and plant origin. This project was carried out to elucidate whether the process of grass pellet production applying hot air drying influences the content of PA and PANO. Samples of hay (n = 22) and grass pellets (n = 28) originated from naturally infested grassland (around 10% and 30% dominance of Senecio aquaticus) and from a trial plot with around 50% dominance. Grass pellets were prepared from grass originating from exactly the same plots as the hay samples. The samples were analysed by liquid chromatography-tandem mass spectrometry for PA/PANO typically produced by this weed. The results of the study revealed that PA/PANO levels (predominantly sum of senecionine, seneciphylline, erucifoline and their N-oxides) in hay ranged between 2.1 and 12.6 mg kg dry matter in samples with 10% and 30% dominance of S. aquaticus, respectively. Samples from the trial plot (50% dominance) had levels of up to 52.9 mg kg . Notably, the hot air drying process during the production of grass pellets did not lead to a reduction of PA/PANO levels. Instead, the levels in grass pellets with 10% and 30% S. aquaticus ranged from 3.1 to 55.1 mg kg . Grass pellets from the trial plot contained up to 96.8 mg kg . In conclusion, hot air drying and grass pellet production did not affect PA/PANO contents in plant material and therefore, heat-dried products cannot be regarded as safe in view of the toxic potential of 1,2-dehydro-pyrrolizidine alkaloids.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180223
[Lr] Last revision date:180223
[St] Status:Publisher
[do] DOI:10.1080/19440049.2018.1430901

  10 / 1931 MEDLINE  
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[PMID]: 29373009
[Au] Autor:Li L; Tang MC; Tang S; Gao S; Soliman S; Hang L; Xu W; Ye T; Watanabe K; Tang Y
[Ad] Address:Engineering Research Center of Industrial Microbiology (Ministry of Education) and College of Life Sciences, Fujian Normal University , Fuzhou 350117, China.
[Ti] Title:Genome Mining and Assembly-Line Biosynthesis of the UCS1025A Pyrrolizidinone Family of Fungal Alkaloids.
[So] Source:J Am Chem Soc;140(6):2067-2071, 2018 Feb 14.
[Is] ISSN:1520-5126
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:UCS1025A is a fungal polyketide/alkaloid that displays strong inhibition of telomerase. The structures of UCS1025A and related natural products are featured by a tricyclic furopyrrolizidine connected to a trans-decalin fragment. We mined the genome of a thermophilic fungus and activated the ucs gene cluster to produce UCS1025A at a high titer. Genetic and biochemical analysis revealed a PKS-NRPS assembly line that activates 2S,3S-methylproline derived from l-isoleucine, followed by Knoevenagel condensation to construct the pyrrolizidine moiety. Oxidation of the 3S-methyl group to a carboxylate leads to an oxa-Michael cyclization and furnishes the furopyrrolizidine. Our work reveals a new strategy used by nature to construct heterocyclic alkaloid-like ring systems using assembly line logic.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180221
[Lr] Last revision date:180221
[St] Status:In-Data-Review
[do] DOI:10.1021/jacs.8b00056


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