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Hepatotoxin

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https://www.readbyqxmd.com/read/29132031/effects-of-microcystis-on-development-of-early-life-stage-japanese-medaka-oryzias-latipes-comparative-toxicity-of-natural-blooms-cultured-microcystis-and-microcystin-lr
#1
Spencer R Saraf, Amy Frenkel, Matthew J Harke, Jennifer G Jankowiak, Christopher J Gobler, Anne E McElroy
Freshwater cyanobacterial harmful algal blooms (CyanoHABs) caused by algae in the genus Microcystis have been increasing in frequency and severity in recent decades. Microcystis blooms threaten aquatic organisms through effects associated with the rapid increase of biomass and the production of the hepatotoxin microcystin (MC) by toxic strains. Among fish, effects of blooms are likely to be more severe for early life stages, and physiological impacts on this life stage could significantly impact recruitment and fish populations...
November 2, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29062311/production-of-high-amounts-of-hepatotoxin-nodularin-and-new-protease-inhibitors-pseudospumigins-by-the-brazilian-benthic-nostoc-sp-cena543
#2
Jouni Jokela, Lassi M P Heinilä, Tânia K Shishido, Matti Wahlsten, David P Fewer, Marli F Fiore, Hao Wang, Esa Haapaniemi, Perttu Permi, Kaarina Sivonen
Nostoc is a cyanobacterial genus, common in soils and a prolific producer of natural products. This research project aimed to explore and characterize Brazilian cyanobacteria for new bioactive compounds. Here we report the production of hepatotoxins and new protease inhibitors from benthic Nostoc sp. CENA543 isolated from a small, shallow, saline-alkaline lake in the Nhecolândia, Pantanal wetland area in Brazil. Nostoc sp. CENA543 produces exceptionally high amounts of nodularin-R. This is the first free-living Nostoc that produces nodularin at comparable levels as the toxic, bloom-forming, Nodularia spumigena...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29055933/long-term-low-dose-exposure-to-microcystin-lr-does-not-cause-or-increase-the-severity-of-liver-disease-in-rodents
#3
Meaghan Labine, Yuewen Gong, Gerald Y Minuk
BACKGROUND: Acute exposure to high concentrations of microcystin-LR (MC-LR) can cause significant hepatocyte injury. AIM: To document the effects of long-term, low-dose MC-LR exposure on hepatic inflammation and fibrosis in mice with healthy and diseased livers. MATERIAL AND METHODS: Male CD1 mice (N = 20/group) were exposed to 1.0 μg/L of MC-LR in drinking water; 1.0 μg/L MC-LR plus 300 mg/L of the hepatotoxin thioacetamide (MC-LR/TAA); or 300 mg/L TAA alone for 28 weeks...
October 16, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/29054145/simple-high-efficiency-detection-of-microcystins-and-nodularin-r-in-water-by-fluorescence-polarization-immunoassay
#4
Huiyan Zhang, Shupeng Yang, Ross C Beier, Natalia V Beloglazova, Hongtao Lei, Xiulan Sun, Yuebin Ke, Suxia Zhang, Zhanhui Wang
This manuscript describes the development of a sensitive, fast and easily-performed fluorescence polarization immunoassay (FPIA) for detection of microcystins (MCs) and nodularin-R (NOD) in water. MCs and NOD, the most widespread cyanobacterial toxin are hepatotoxins and tumor promoters, and their acute exposure may result in severe health problems in animals and humans. The fluorescein-based tracers were synthesized, and for the first time preparative high performance liquid chromatography (HPLC) was employed for their purification...
November 1, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29024253/prerequisites-of-isopeptide-bond-formation-in-microcystin-biosynthesis
#5
Sabine Meyer, Andi Mainz, Jan-Christoph Kehr, Roderich D Süssmuth, Elke Dittmann
The biosynthesis of the potent cyanobacterial hepatotoxin microcystin involves isopeptide bond formation through the carboxylic acid side chains of d-glutamate and β-methyl d-aspartate. Analysis of the in vitro activation profiles of the two corresponding adenylation domains, McyE-A and McyB-A2 , either in a didomain or a tridomain context with the cognate thiolation domain and the upstream condensation domain revealed that substrate activation of both domains strictly depended on the presence of the condensation domains...
October 11, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28984034/microcystin-lr-disrupts-insulin-signaling-by-hyperphosphorylating-insulin-receptor-substrate-1-and-glycogen-synthase
#6
Jinghui Liu, Chun Xu, Shaofeng Zhang, Haoyan Li, Kele Chen, Pu Huang, Zonglou Guo, Lihong Xu
Microcystin-LR (MC-LR) is a cyanobacteria-derived heptapeptide that has been commonly characterized as a hepatotoxin. Although the liver is a primary organ in glucose homeostasis, the effect of MC-LR on glucose metabolism remains unclear. In this study, the human liver cell line HL7702 and ICR mice were exposed to various concentrations of MC-LR for 24 h, and the proteins involved in insulin signaling were investigated. The results showed that MC-LR treatment induced the hyperphosphorylation of insulin receptor substrate 1 (IRS1) at several serine sites, S307, S323, S636/639, and S1101 in HL7702 cells, and S302, S318, S632/635, and S1097 in mice livers...
October 6, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28919358/perfused-human-hepatocyte-microtissues-identify-reactive-metabolite-forming-and-mitochondria-perturbing-hepatotoxins
#7
Cliff Rowe, Mohsen Shaeri, Emma Large, Terri Cornforth, Angela Robinson, Tomasz Kostrzewski, Rowena Sison-Young, Christopher Goldring, Kevin Park, David Hughes
Hepatotoxins cause liver damage via many mechanisms but the formation of reactive metabolites and/or damage to liver mitochondria are commonly implicated. We assess 3D human primary hepatocyte microtissues as a platform for hepatotoxicity studies with reactive metabolite-forming and mitochondria-perturbing compounds. We show that microtissues formed from cryopreserved human hepatocytes had bile canaliculi, transcribed mRNA from genes associated with xenobiotic metabolism and expressed functional cytochrome P450 enzymes...
September 15, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28899665/toxin-composition-of-the-2016-microcystis-aeruginosa-bloom-in-the-st-lucie-estuary-florida
#8
Stuart Oehrle, Marliette Rodriguez-Matos, Michael Cartamil, Cristian Zavala, Kathleen S Rein
A bloom of the cyanobacteria, Microcystis aeruginosa occurred in the St. Lucie Estuary during the summer of 2016, stimulated by the release of waters from Lake Okeechobee. This cyanobacterium produces the microcystins, a suite of heptapeptide hepatotoxins. The toxin composition of the bloom was analyzed and was compared to an archived bloom sample from 2005. Microcystin-LR was the most abundant toxin with lesser amounts of microcystin variants. Nodularin, cylindrospermopsin and anatoxin-a were not detected.
November 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28895936/rapid-and-highly-sensitive-non-competitive-immunoassay-for-specific-detection-of-nodularin
#9
Sultana Akter, Markus Vehniäinen, Harri T Kankaanpää, Urpo Lamminmäki
Nodularin (NOD) is a cyclic penta-peptide hepatotoxin mainly produced by Nodularia spumigena, reported from the brackish water bodies of various parts of the world. It can accumulate in the food chain and, for safety reasons, levels of NOD not only in water bodies but also in food matrices are of interest. Here, we report on a non-competitive immunoassay for the specific detection of NOD. A phage display technique was utilized to interrogate a synthetic antibody phage library for binders recognizing NOD bound to an anti-ADDA (3-Amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4(E),6(E)-dienoic acid) monoclonal antibody (Mab)...
September 12, 2017: Microorganisms
https://www.readbyqxmd.com/read/28873456/molecular-prediction-of-lytic-vs-lysogenic-states-for-microcystis-phage-metatranscriptomic-evidence-of-lysogeny-during-large-bloom-events
#10
Joshua M A Stough, Xiangming Tang, Lauren E Krausfeldt, Morgan M Steffen, Guang Gao, Gregory L Boyer, Steven W Wilhelm
Microcystis aeruginosa is a freshwater bloom-forming cyanobacterium capable of producing the potent hepatotoxin, microcystin. Despite increased interest in this organism, little is known about the viruses that infect it and drive nutrient mobilization and transfer of genetic material between organisms. The genomic complement of sequenced phage suggests these viruses are capable of integrating into the host genome, though this activity has not been observed in the laboratory. While analyzing RNA-sequence data obtained from Microcystis blooms in Lake Tai (Taihu, China), we observed that a series of lysogeny-associated genes were highly expressed when genes involved in lytic infection were down-regulated...
2017: PloS One
https://www.readbyqxmd.com/read/28866331/microcystin-lr-exposure-induces-oxidative-damage-in-caenorhabditis-elegans-protective-effect-of-lutein-extracted-from-marigold-flowers
#11
Paula Rossini Augusti, Allana Von Sulzback Brasil, Caroline Souto, Gabriela Göethel, Alessandro de Oliveira Rios, Tatiana Emanuelli, Marilise Escobar Bürger, Solange Cristina Garcia
Microcystin-LR (MIC-LR) is a hepatotoxin, with toxicity mechanisms linked to oxidative stress. Besides, neurotoxic effects of MIC-LR have recently been described. Herein, we evaluated the effects of environmentally important concentrations of MIC-LR (1, 10, 100, 250, and 500 μg/L) on oxidative stress markers and the survival rate of the nematode Caenorhabditis elegans (C. elegans). In addition, a possible protective effect of the carotenoid lutein (LUT) extracted from marigold flowers against MIC-LR toxicity was investigated...
August 31, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28802237/umbelliferon-%C3%AE-d-glucopyranosyl-2-i-%C3%A2-1-ii-%C3%AE-dglucopyranoside-ameliorates-diethylnitrosamine-induced-precancerous-lesion-development-in-liver-via-regulation-of-inflammation-hyperproliferation-and-antioxidant-at-pre-clinical-stage
#12
Vikas Kumar, Prakash Chandra Bhatt, Mahfoozur Rahman, Fahad A Al-Abbasi, Firoz Anwar, Amita Verma
It is well documented that anomalous production of inflammatory proteins linked with most of the toxic expression and genesis of diverse chronic disease including cancer. Diethylnitrosamine (DEN) a well-known hepatotoxin and hepatocarcinogen, can induce oxidative stress and inflammatory reaction in it. Umbelliferone, secondary metabolites, is present in different plants and widely consumed by humans as medicine and food supplements. The aim of the current study was to scrutinize the chemoprotective potential of umbelliferon-α-d-glucopyranosyl-(2(I)→1(II))-α-d-glucopyranoside (UFD) against DEN-induced hepatocellular carcinoma (HCC) in experimental rats...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28801990/degradation-of-euptox-a-by-tannase-producing-rumen-bacteria-from-migratory-goats
#13
D Sharma, G Mal, A Kannan, R Bhar, R Sharma, B Singh
AIMS: The gut microbiota capable of degrading plant biomass and antinutritional phytometabolites are of immense importance. This study reports isolation and characterization of tannase-producing rumen bacteria that could also degrade euptox A (9-oxo-10,11-dehydroageraphorone) present in Eupatorium adenophorum (Spreng). METHODS AND RESULTS: Migratory Gaddi goats were selected as source of inoculums for isolating rumen bacteria with ability to produce tannase which catalyses degradation of hydrolysable tannins (HTs)...
August 12, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28800171/antioxidant-protection-by-%C3%AE-selenoamines-against-thioacetamide-induced-oxidative-stress-and-hepatotoxicity-in-mice
#14
Sílvio Terra Stefanello, Diane Duarte Hartmann, Guilherme Pires Amaral, Aline Alves Courtes, Martim T B Leite, Thayanara Cruz da Silva, Débora Farina Gonçalves, Micaela B Souza, Pâmela Carvalho da Rosa, Luciano Dornelles, Félix Alexandre Antunes Soares
Thioacetamide (TAA) is a hepatotoxin that rapidly triggers the necrotic process and oxidative stress in the liver. Nevertheless, organic selenium compounds, such as β-selenoamines, can be used as pharmacological agents to diminish the oxidative damage. Thus, the aim of this study was to investigate the protective effect of the antioxidant β-selenoamines on TAA-induced oxidative stress in mice. Here, we observed that a single intraperitoneal injection of TAA (200 mg/kg) dramatically elevated some parameters of oxidative stress, such as lipid peroxidation and reactive oxygen species (ROS) production, as well as depleted cellular antioxidant defenses...
August 11, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28772230/the-biodegradation-of-microcystins-in-temperate-freshwater-bodies-with-previous-cyanobacterial-history
#15
Dariusz Dziga, Anna Maksylewicz, Magdalena Maroszek, Agnieszka Budzyńska, Agnieszka Napiorkowska-Krzebietke, Magdalena Toporowska, Magdalena Grabowska, Anna Kozak, Joanna Rosińska, Jussi Meriluoto
Cyanobacterial blooms and cyanotoxins occur in freshwater lakes and reservoirs all over the world. Bacterial degradation of microcystins (MC), hepatotoxins produced by several cyanobacterial species, has also been broadly documented. However, information regarding MC biodegradation in European water bodies is very limited. In this paper, the occurrence and identification of MC biodegradation products was documented for 21 European lakes and reservoirs, many of which have well-documented cyanobacterial bloom histories...
July 31, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28772086/highlights-of-drug-and-herb-induced-liver-injury-in-the-literature-from-2016-how-best-to-translate-new-information-into-clinical-practice
#16
REVIEW
Omar Shahbaz, Sandeep Mahajan, James H Lewis
Over 1500 papers on drug-induced liver injury (DILI) and herb-induced liver injury (HILI) were published in 2016, many of which have the potential to impact clinical practice. Areas covered: Clinical studies and case series that lent themselves to new concepts in diagnosing, and treating DILI were selected for inclusion. Epidemiology of DILI in large prospective registries was highlighted. Causality assessment of drug hepatotoxicity remains challenging, as seen with cases of OxyELITE Pro (OEP). In 2016 updates to the Roussel Uclaf Causality Assessment Method (RUCAM) were published to aid in the accuracy of diagnosing DILI/HILI...
September 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28765097/selenium-triggers-nrf2-mediated-protection-against-cadmium-induced-chicken-hepatocyte-autophagy-and-apoptosis
#17
Cong Zhang, Jia Lin, Jing Ge, Li-Li Wang, Nan Li, Xue-Tong Sun, Hua-Bin Cao, Jin-Long Li
Cadmium (Cd) is a ubiquitously distributed trace metal and environmental pollutant that is highly toxic to liver. Selenium (Se) may provide chemoprotection against Cd-induced cytotoxicity by augmenting the cellular antioxidant capacity. However, the mechanism of Se chemoprotection against Cd-induced hepatotoxicity is unclear. The present study evaluated the ameliorative properties of Se against Cd-induced cytotoxicity in hepatocytes. Primary cells were exposed to 5μM Cd and/or 1μM Se for 24h. Cellular morphology and function, antioxidant status, activation of Nrf2 pathway, autophagy and apoptosis were determined...
October 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28763935/parental-exposure-to-microcystin-lr-induced-thyroid-endocrine-disruption-in-zebrafish-offspring-a-transgenerational-toxicity
#18
Houcheng Cheng, Wei Yan, Qin Wu, Chunsheng Liu, Xiuying Gong, Tien-Chieh Hung, Guangyu Li
Microcystin-LR is the most poisonous and commonly encountered hepatotoxin produced by cyanobacteria in an aquatic ecosystem, and it may cause thyroid dysfunction in fish. The present study aimed to reveal the effects of transgenerational toxicity of MCLR on the thyroid endocrine system under sub-chronic exposure conditions. Adult zebrafish (F0) were exposed to environmentally relevant concentrations (1, 5 and 25 μg/L) of MCLR for 45 days. The produced F1 embryos were then tested without further MCLR treatment...
November 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28758069/investigating-the-application-of-a-nitroreductase-expressing-transgenic-zebrafish-line-for-high-throughput-toxicity-testing
#19
Anna C Chlebowski, Jane K La Du, Lisa Truong, Staci L Massey Simonich, Robert L Tanguay
Nitroreductase enzymes are responsible for the reduction of nitro functional groups to amino functional groups, and are found in a range of animal models, zebrafish (Danio rerio) excluded. Transgenic zebrafish models have been developed for tissue-specific cell ablation, which use nitroreductase to ablate specific tissues or cell types following exposure to the non-toxic pro-drug metronidazole (MTZ). When metabolized by nitroreductase, MTZ produces a potent cytotoxin, which specifically ablates the tissue in which metabolism occurs...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28737704/toxicity-at-the-edge-of-life-a-review-on-cyanobacterial-toxins-from-extreme-environments
#20
REVIEW
Samuel Cirés, María Cristina Casero, Antonio Quesada
Cyanotoxins are secondary metabolites produced by cyanobacteria, of varied chemical nature and toxic effects. Although cyanobacteria thrive in all kinds of ecosystems on Earth even under very harsh conditions, current knowledge on cyanotoxin distribution is almost restricted to freshwaters from temperate latitudes. In this review, we bring to the forefront the presence of cyanotoxins in extreme environments. Cyanotoxins have been reported especially in polar deserts (both from the Arctic and Antarctica) and alkaline lakes, but also in hot deserts, hypersaline environments, and hot springs...
July 24, 2017: Marine Drugs
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