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https://www.readbyqxmd.com/read/28919358/perfused-human-hepatocyte-microtissues-identify-reactive-metabolite-forming-and-mitochondria-perturbing-hepatotoxins
#1
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
#2
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.
September 9, 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
#3
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
#4
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
#5
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
#6
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
#7
D Sharma, G Mal, A Kannan, R Bhar, R Sharma, B Singh
AIMS: The gut microbiota capable of degrading plant biomass and anti-nutritional 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 catalyzes 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
#8
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
#9
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
#10
Omar Shahbaz, Sandeep Mahajan, James H Lewis
INTRODUCTION: More than 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 or directions in diagnosing, preventing, and treating DILI were selected for inclusion. Epidemiology of DILI in large prospective registries was highlighted, including the US DILIN network and Spanish DILI registry...
August 3, 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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28648459/acute-liver-failure-is-associated-with-altered-cerebral-expression-profiles-of-long-non-coding-rnas
#15
Vinícius R Silva, Rodrigo Secolin, Raghu Vemuganti, Iscia Lopes-Cendes, Alan S Hazell
Hepatic encephalopathy (HE) represents a serious complication of acute liver failure (ALF) in which cerebral edema leading to brainstem herniation as a result of increased intracranial hypertension is a major consequence. Long non-coding RNAs (lncRNAs) play a significant role in coordinating gene expression, with recent studies indicating an influence in the pathogenesis of several diseases. To investigate their involvement in the cerebral pathophysiology of ALF, we profiled the expression of lncRNAs in the frontal cortex of mice at coma stage following treatment with the hepatotoxin azoxymethane...
June 23, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28646179/herbal-medicine-yinchenhaotang-protects-against-%C3%AE-naphthylisothiocyanate-induced-cholestasis-in-rats
#16
Jingyu Yan, Guoxiang Xie, Chungeng Liang, Yiyang Hu, Aihua Zhao, Fengjie Huang, Ping Hu, Ping Liu, Wei Jia, Xiaoning Wang
Cholestasis is a clinical disorder defined as an impairment of bile flow, and that leads to toxic bile acid (BA) accumulation in hepatocytes. Here, we investigated the hepatoprotective effect of Yinchenhaotang (YCHT), a well-known formulae for the treatment of jaundice and liver disorders, against the cholestasis using the α-naphthylisothiocyanate (ANIT)-induced cholestasis in male Wistar rats. ANIT feeding induced significant cholestasis with substantially increased intrahepatic retention of hydrophobic BAs...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634756/a-high-throughput-targeted-and-non-targeted-method-for-the-analysis-of-microcystins-and-anatoxin-a-using-on-line-solid-phase-extraction-coupled-to-liquid-chromatography-quadrupole-time-of-flight-high-resolution-mass-spectrometry
#17
Xavier Ortiz, Eva Korenkova, Karl J Jobst, Karen A MacPherson, Eric J Reiner
Microcystins are cyclic heptapeptide hepatotoxins produced by cyanobacteria in freshwater. Sample preparation for the analysis of these cyanotoxins in water from algal blooms can take up to several days due to the matrix complexity and the low detection limits required to comply with current legislation. Moreover, there is a large number of unknown microcystins that could potentially exist in the environment resulting from different amino acid substitutions into the microcystin skeletal structure. To tackle these problems, the present study involved the development of a high throughput method based on on-line solid phase extraction coupled to liquid chromatography that could provide quantitative results for 12 microcystin variants (LR, YR, RR, HtyR, HilR, WR, LW, LA, LF, LY, Dha(7)-LR, and Dha(7)-RR) and anatoxin-A in less than 3 h with detection limits between 0...
August 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28606423/unraveling-the-presence-of-multi-class-toxins-from-trichodesmium-bloom-in-the-gulf-of-mannar-region-of-the-bay-of-bengal
#18
Sumathy Shunmugam, Manickam Gayathri, Nainangu Prasannabalaji, Nooruddin Thajuddin, Gangatharan Muralitharan
Trichodesmium is an enigmatic bloom forming, non-heterocystous cyanobacterium reported most frequently in the coastal waters of India. However, the toxigenic potential of this globally significant N2 fixing cyanobacterium has not been characterized. In this study, we report for the first time the presence of potent multi-class neurotoxins such as Anatoxin-a, Saxitoxins, Gonyautoxin and hepatotoxins like MC-LR, MC-YA from a bloom material of Trichodesmium sp. MBDU 524 collected at the Gulf of Mannar region. Toxins were determined using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) analysis of HPLC purified aqueous and solvent fractions...
June 9, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28594241/hepatotoxicity-evaluation-of-traditional-chinese-medicines-using-a-computational-molecular-model
#19
Pan Zhao, Bin Liu, Chunya Wang
BACKGROUND: Liver injury caused by traditional Chinese medicines (TCMs) is reported from many countries around the world. TCM hepatotoxicity has attracted worldwide concerns. OBJECTIVE: This study aims to develop a more applicable and optimal tool to evaluate TCM hepatotoxicity. METHODS: A quantitative structure-activity relationship (QSAR) analysis was performed based on published data and U.S. Food and Drug Administration's Liver Toxicity Knowledge Base (LTKB)...
November 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28585115/cyanobacterial-neurotoxins-their-occurrence-and-mechanisms-of-toxicity
#20
Kenneth J Rodgers, Brendan J Main, Kate Samardzic
Cyanobacteria are some of the oldest organisms on earth, and have evolved to produce a battery of toxic metabolites, including hepatotoxins, dermatoxins, and neurotoxins. In this review, we focus on the occurrence and mechanisms of toxicity of a number of neurotoxins synthesised by these ancient photosynthetic prokaryotes. We discuss the evidence linking β-methylamino-L-alanine (BMAA), a non-protein amino acid, to an unusual neurological disease complex reported on the island of Guam in the 1950s, and how 60 years later, the role that BMAA plays in human disease is still unclear...
June 5, 2017: Neurotoxicity Research
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