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Hepatotoxin

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https://www.readbyqxmd.com/read/28648459/acute-liver-failure-is-associated-with-altered-cerebral-expression-profiles-of-long-non-coding-rnas
#1
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 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28646179/herbal-medicine-yinchenhaotang-protects-against-%C3%AE-naphthylisothiocyanate-induced-cholestasis-in-rats
#2
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
#3
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...
June 20, 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
#4
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
#5
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)...
June 8, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28585115/cyanobacterial-neurotoxins-their-occurrence-and-mechanisms-of-toxicity
#6
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
https://www.readbyqxmd.com/read/28573132/prebiotics-a-novel-approach-to-treat-hepatocellular-carcinoma
#7
REVIEW
Naz Fatima, Tasleem Akhtar, Nadeem Sheikh
Hepatocellular carcinoma is one of the fatal malignancies and is considered as the third leading cause of death. Mutations, genetic modifications, dietary aflatoxins, or impairments in the regulation of oncogenic pathways may bring about liver cancer. An effective barrier against hepatotoxins is offered by gut-liver axis as a change in gut permeability and expanded translocation of lipopolysaccharides triggers the activation of Toll-like receptors which stimulate the process of hepatocarcinogenesis. Prebiotics, nondigestible oligosaccharides, have a pivotal role to play when it comes to inducing an antitumor effect...
2017: Canadian Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28552552/b-13-progenitor-derived-hepatocytes-b-13-h-cells-model-lipid-dysregulation-in-response-to-drugs-and-chemicals
#8
Alistair C Leitch, Philip M E Probert, James A Shayman, Stephanie K Meyer, George E N Kass, Matthew C Wright
Lipid dysregulation is a common hepatic adverse outcome after exposure to toxic drugs and chemicals. A donor-free rat hepatocyte-like (B-13/H) cell was therefore examined as an in vitro model for investigating mechanisms. The B-13/H cell irreversibly accumulated triglycerides (steatosis) in a time- and dose-dependent manner when exposed to fatty acids, an effect that was potentiated by the combined addition of hyperglycaemic levels of glucose and insulin. B-13/H cells also expressed the LXR nuclear receptors and exposure to their activators - T0901317 or GW3965 - induced luciferase expression from a transfected LXR-regulated reporter gene construct and steatosis in a dose-dependent manner with T0901317...
May 25, 2017: Toxicology
https://www.readbyqxmd.com/read/28544902/extraction-and-applications-of-cyanotoxins-and-other-cyanobacterial-secondary-metabolites
#9
REVIEW
Fatima Haque, Sara Banayan, Josephine Yee, Yi Wai Chiang
The rapid proliferation of cyanobacteria in bodies of water has caused cyanobacterial blooms, which have become an increasing cause of concern, largely due to the presence of toxic secondary metabolites (or cyanotoxins). Cyanotoxins are the toxins produced by cyanobacteria that may be harmful to surrounding wildlife. They include hepatotoxins, neurotoxins and dermatotoxins, and are classified based on the organs they affect. There are also non-toxic secondary metabolites that include chelators and UV-absorbing compounds...
May 18, 2017: Chemosphere
https://www.readbyqxmd.com/read/28529062/quantitative-targeted-bile-acid-profiling-as-new-markers-for-dili-in-a-model-of-methapyrilene-induced-liver-injury-in-rats
#10
Markus Slopianka, Anne Herrmann, Mira Pavkovic, Heidrun Ellinger-Ziegelbauer, Rainer Ernst, Angela Mally, Matthias Keck, Bjoern Riefke
Recently, bile acids (BAs) were reported as promising markers for drug-induced liver injury (DILI). BAs have been suggested to correlate with hepatocellular and hepatobiliary damage; however a clear connection of BA patterns with different types of DILI remains to be established. To investigate if BAs can improve the assessment of liver injury, 20 specific BAs were quantitatively profiled via LC-MS/MS in plasma and liver tissue in a model of methapyrilene-induced liver injury in rats. Methapyrilene, a known hepatotoxin was dosed daily over 14-days at doses of 30 and 80mg/kg, followed by a recovery phase of 10days...
May 19, 2017: Toxicology
https://www.readbyqxmd.com/read/28521788/methanol-extract-of-dicranopteris-linearis-l-leaves-impedes-acetaminophen-induced-liver-intoxication-partly-by-enhancing-the-endogenous-antioxidant-system
#11
Zainul Amiruddin Zakaria, Farah Hidayah Kamisan, Maizatul Hasyima Omar, Nur Diyana Mahmood, Fezah Othman, Siti Selina Abdul Hamid, Muhammad Nazrul Hakim Abdullah
BACKGROUND: The present study investigated the potential of methanolic extract of Dicranopteris linearis (MEDL) leaves to attenuate liver intoxication induced by acetaminophen (APAP) in rats. METHODS: A group of mice (n = 5) treated orally with a single dose (5000 mg/kg) of MEDL was first subjected to the acute toxicity study using the OECD 420 model. In the hepatoprotective study, six groups of rats (n = 6) were used and each received as follows: Group 1 (normal control; pretreated with 10% DMSO (extract's vehicle) followed by treatment with 10% DMSO (hepatotoxin's vehicle) (10% DMSO +10% DMSO)), Group 2 (hepatotoxic control; 10% DMSO +3 g/kg APAP (hepatotoxin)), Group 3 (positive control; 200 mg/kg silymarin +3 g/kg APAP), Group 4 (50 mg/kg MEDL +3 g/kg APAP), Group 5 (250 mg/kg MEDL +3 g/kg APAP) or Group 6 (500 mg/kg MEDL +3 g/kg APAP)...
May 18, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28515612/acute-yellow-phosphorus-poisoning-causing-fulminant-hepatic-failure-with-parenchymal-hemorrhages-and-contained-duodenal-perforation
#12
Reddy Ravikanth, S Sandeep, Babu Philip
White phosphorus is well known as a potent hepatotoxin and a severe local and systemic toxin causing damage to gastrointestinal, hepatic, cardiovascular, and renal systems. It is used in the manufacture of matches, fireworks, rodenticide, and fertilizers. Death results due to acute liver failure. Management of yellow phosphorus (YP) poisoning is supportive with no antidote available. Here, we present a case of acute YP poisoning in a 25-year-old female presenting with fulminant hepatic failure and duodenal perforation...
April 2017: Indian Journal of Critical Care Medicine
https://www.readbyqxmd.com/read/28494149/comparison-of-three-antihapten-vhh-selection-strategies-for-the-development-of-highly-sensitive-immunoassays-for-microcystins
#13
Macarena Pírez-Schirmer, Martín Rossotti, Natalia Badagian, Carmen Leizagoyen, Beatriz M Brena, Gualberto González-Sapienza
Owing to their reproducibility, stability, and cost-effective production, the recombinant variable domains of heavy-chain-only antibodies (VHHs) are becoming a salient option as immunoassay reagents. Recently, there have been several reports describing their application to the detection of small molecules (haptens). However, lacking the heavy-light chain interface of conventional antibodies, VHHs are not particularly apt to bind small analytes and failures are not uncommon. Here we describe the construction of a VHH phage display library against the cyanobacterial hepatotoxin microcystin LR and its selection using competitive panning and two novel panning strategies...
June 2, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28429062/detection-of-freshwater-cyanotoxins-and-measurement-of-masked-microcystins-in-tilapia-from-southeast-asian-aquaculture-farms
#14
Brett Greer, Ronald Maul, Katrina Campbell, Christopher T Elliott
Recently, there has been a rise in freshwater harmful algal blooms (HABs) globally, as well as increasing aquaculture practices. HABs can produce cyanotoxins, many of which are hepatotoxins. An ultra-performance liquid chromatography tandem mass spectrometry method was developed and validated for nine cyanotoxins across three classes including six microcystins, nodularin, cylindrospermopsin and anatoxin-a. The method was used to analyse free cyanotoxin(s) in muscle (n = 34), liver (n = 17) and egg (n = 9) tissue samples of 34 fish sourced from aquaculture farms in Southeast Asia...
June 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28409869/single-and-combined-effects-of-microcystin-and-saxitoxin-producing-cyanobacteria-on-the-fitness-and-antioxidant-defenses-of-cladocerans
#15
Aloysio da S Ferrão-Filho, Daniel de Abreu S Silva, Taissa A de Oliveira, Valéria Freitas de Magalhães, Stephan Pflugmacher, Eduardo Mendes da Silva
Cyanobacteria produce different toxic compounds that affect animal life, among them hepatotoxins and neurotoxins. Because cyanobacteria are able to produce a variety of toxic compounds at the same time, organisms may be, generally, subjected to their combined action. In the present study, we demonstrate the single and combined effects on cladocerans of cyanobacteria that produce microcystins (hepatotoxins) and saxitoxins (neurotoxins). Animals were exposed (either singly or combined) to 2 strains of cyanobacteria isolated from the same environment (Funil Reservoir, Rio de Janeiro, Brazil)...
April 14, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28369597/exploring-chronic-drug-effects-on-microengineered-human-liver-cultures-using-global-gene-expression-profiling
#16
Brenton R Ware, Michael McVay, Wendy Y Sunada, Salman R Khetani
Global gene expression profiling is useful for elucidating a drug's mechanism of action (MOA) on the liver; however, such profiling in rats is not very sensitive for predicting human drug-induced liver injury, while de-differentiated monolayers of primary human hepatocytes (PHHs) do not permit chronic drug treatment. In contrast, micropatterned co-cultures (MPCCs) containing PHH colonies and 3T3-J2 fibroblasts maintain a stable liver phenotype for 4-6 weeks. Here, we used MPCCs to test the hypothesis that global gene expression patterns in stable PHHs can be used to distinguish clinical hepatotoxic drugs from their non-liver-toxic analogs and understand the MOA prior to the onset of overt hepatotoxicity...
March 24, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28330995/hepatic-fcrn-regulates-albumin-homeostasis-and-susceptibility-to-liver-injury
#17
Michal Pyzik, Timo Rath, Timothy T Kuo, Sanda Win, Kristi Baker, Jonathan J Hubbard, Rosa Grenha, Amit Gandhi, Thomas D Krämer, Adam R Mezo, Zachary S Taylor, Kevin McDonnell, Vicki Nienaber, Jan Terje Andersen, Atsushi Mizoguchi, Laurence Blumberg, Shalaka Purohit, Susan D Jones, Greg Christianson, Wayne I Lencer, Inger Sandlie, Neil Kaplowitz, Derry C Roopenian, Richard S Blumberg
The neonatal crystallizable fragment receptor (FcRn) is responsible for maintaining the long half-life and high levels of the two most abundant circulating proteins, albumin and IgG. In the latter case, the protective mechanism derives from FcRn binding to IgG in the weakly acidic environment contained within endosomes of hematopoietic and parenchymal cells, whereupon IgG is diverted from degradation in lysosomes and is recycled. The cellular location and mechanism by which FcRn protects albumin are partially understood...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28330766/water-metabolism-dysfunction-via-renin-angiotensin-system-activation-caused-by-liver-damage-in-mice-treated-with-microcystin-rr
#18
Qing Zhong, Feng Sun, Weiguang Wang, Wenqing Xiao, Xiaoni Zhao, Kangding Gu
Microcystins (MCs) are a group of monocyclic heptapeptide toxins that have been shown to act as potent hepatotoxins. However, the observed symptoms of water metabolism disruption induced by microcystin-RR (MC-RR) or MCs have rarely been reported, and a relatively clear mechanism has not been identified. In the present study, male mice were divided into 4 groups (A: 140μg/kg, B: 70μg/kg,C: 35μg/kg, and D: 0μg/kg) and administered MC-RR daily for a month. On day 8 of treatment, an increase in water intake and urine output was observed in the high-dose group compared with the control, and the symptoms worsened with the repeated administration of the toxin until day 30...
May 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28324259/protective-effect-of-nigella-sativa-seeds-against-spermatocyte-chromosomal-aberrations-and-genotoxicity-induced-by-carbon-tetrachloride-in-mice
#19
Ashraf M Abdel-Moneim, Amina E Essawy, Sherifa S Hamed, Ashgan A Abou-Gabal, Aglal A Alzergy
Nigella sativa is a well-known dietary antioxidant and a valuable inhibitor of clastogenesis and carcinogenesis. The purpose of the present work was to investigate the effects of N. sativa seeds against chromosomal aberrations in primary spermatocytes and early embryonic lethality induced by CCl4 hepatotoxin in Swiss albino mice. One hundred male Swiss albino mice were randomly divided into five groups. Groups I, II, and III received only normal saline, olive oil, and aqueous suspension of N. sativa seeds (50 mg/kg b...
April 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28282614/inhibition-of-drp1-protects-against-senecionine-induced-mitochondria-mediated-apoptosis-in-primary-hepatocytes-and-in-mice
#20
Xiao Yang, Hua Wang, Hong-Min Ni, Aizhen Xiong, Zhengtao Wang, Hiromi Sesaki, Wen-Xing Ding, Li Yang
Pyrrolizidine alkaloids (PAs) are a group of compounds found in various plants and some of them are widely consumed in the world as herbal medicines and food supplements. PAs are potent hepatotoxins that cause irreversible liver injury in animals and humans. However, the mechanisms by which PAs induce liver injury are not clear. In the present study, we determined the hepatotoxicity and molecular mechanisms of senecionine, one of the most common toxic PAs, in primary cultured mouse and human hepatocytes as well as in mice...
August 2017: Redox Biology
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