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Hepatotoxin

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https://www.readbyqxmd.com/read/28429062/detection-of-freshwater-cyanotoxins-and-measurement-of-masked-microcystins-in-tilapia-from-southeast-asian-aquaculture-farms
#1
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...
April 20, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28409869/single-and-combined-effects-of-microcystins-and-saxitoxins-producer-cyanobacteria-on-the-fitness-and-antioxidant-defenses-of-cladocerans
#2
Aloysio da S Ferrão-Filho, Daniel Abreu S de 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. As 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 effects of single and combined hepatotoxic (microcystins) and neurotoxic (saxitoxins) producer cyanobacteria on cladocerans. Animals were exposed to two strains of cyanobacteria isolated from the same environment (Funil Reservoir, RJ), either in single or combined exposures...
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
#3
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
#4
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
#5
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...
March 19, 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
#6
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...
March 21, 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
#7
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...
March 2, 2017: Redox Biology
https://www.readbyqxmd.com/read/28273397/associations-of-cyp2c9-and-cyp2a6-polymorphisms-with-the-concentrations-of-valproate-and-its-hepatotoxin-metabolites-and-vpa-induced-hepatotoxicity
#8
Mingming Zhao, Ti Zhang, Guofei Li, Feng Qiu, Yaxin Sun, Limei Zhao
The aim of this study was to compare genetic polymorphisms and concentrations of hepatotoxic metabolites in patients with epilepsy and liver injury and those with normal liver function receiving valproate monotherapy to identify risk factors for VPA-induced hepatotoxicity. A total of 279 Chinese patients with epilepsy were divided into an abnormal liver function (ANLFT) group (n=79) and a normal liver function (NLFT) group (n=200). PCR-RFLP, nested-PCR and direct sequencing were applied to identify the frequency of 8 SNPs in candidate genes...
March 8, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28263459/intrahepatic-sampling-for-the-elucidation-of-antiviral-clinical-pharmacology
#9
Charles S Venuto, Andrew H Talal
Although the importance of the liver in clinical pharmacology is widely recognized, little is known in humans concerning its function in vivo at the hepatocyte level and how pharmacological functions are altered in the setting of advanced liver disease. Several recent proof-of-principle studies with first-generation DAAs have demonstrated the feasibility of serial liver sampling for pharmacological studies. These studies have begun to describe the liver-to-plasma concentration ratio and how this ratio is altered in the setting of advanced liver disease...
March 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28193586/influence-of-cuso4-and-chelated-copper-algaecide-exposures-on-biodegradation-of-microcystin-lr
#10
Kyla J Iwinski, John H Rodgers, Ciera M Kinley, Maas Hendrikse, Alyssa J Calomeni, Andrew D McQueen, Tyler D Geer, Jenny Liang, Vanessa Friesen, Monique Haakensen
Copper exposures from algaecide applications in aquatic systems are hypothesized to impede bacterial degradation of microcystin (MC), a cyanobacterial produced hepatotoxin. Despite regulatory implications of this hypothesis, limited data exist on influences of copper-exposures on MC-degrading bacteria and consequent MC-degradation. In this study, influences of copper-algaecide concentrations and formulations on bacterial composition and microcystin-LR (MCLR) degradation were investigated. Microcystis aeruginosa was exposed to four concentrations (0-5...
May 2017: Chemosphere
https://www.readbyqxmd.com/read/28177690/ciliary-neurotrophic-factor-analogue-aggravates-ccl4-induced-acute-hepatic-injury-in-rats
#11
Ming-Xia Cui, Jun-Feng Jiang, Guang-Ning Min, Wei Han, Yong-Jie Wu
Ciliary neurotrophic factor (CNTF) and CNTF analogs were reported to have hepatoprotective effect and ameliorate hepatic steatosis in db/db or high-fat-diet-fed mice. Because hepatic steatosis and injury are also commonly induced by hepatotoxin, the aim of the present study is to clarify whether CNTF could alleviate hepatic steatosis and injury induced by carbon tetrachloride (CCl4). Unexpectedly, when combined with CCl4, CNTF aggravated hepatic steatosis and liver injury. The mechanism is associated with effects of CNTF that inhibited lipoprotein secretion and drastically impaired the ability of lipoproteins to act as transport vehicles for lipids from the liver to the circulation...
May 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28163251/overexpression-of-carboxylesterase-contributes-to-the-attenuation-of-cyanotoxin-microcystin-lr-toxicity
#12
Shota Takumi, Tai Shimono, Satoshi Ikema, Yuki Hotta, Petros K Chigwechokha, Kazuhiro Shiozaki, Yasumasa Sugiyama, Mitsuru Hashimoto, Tatsuhiko Furukawa, Masaharu Komatsu
Microcystin-LR is a hepatotoxin produced by several cyanobacteria. Its toxicity is mainly due to a inhibition of protein phosphatase, PP1 and PP2A. Previously, we used a cell line stably expressing uptake transporter for microcystin-LR, OATP1B3 (HEK293-OATP1B3 cells). In this study, to determine whether overexpression of carboxylesterase (CES), which degrades ester-group and amide-group, attenuates the cytotoxicity of microcystin-LR, we generated the HEK293-OATP1B3/CES2 double-transfected cells. HEK293-OATP1B3/CES2 cells showed high hydrolysis activity of p-nitrophenyl acetate (PNPA), which is an authentic substrate for esterase...
April 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28120901/patient-specific-hepatocyte-like-cells-derived-from-induced-pluripotent-stem-cells-model-pazopanib-mediated-hepatotoxicity
#13
Yukti Choudhury, Yi Chin Toh, Jiangwa Xing, Yinghua Qu, Jonathan Poh, Li Huan, Hui Shan Tan, Ravindran Kanesvaran, Hanry Yu, Min-Han Tan
Idiosyncratic drug-induced hepatotoxicity is a major cause of liver damage and drug pipeline failure, and is difficult to study as patient-specific features are not readily incorporated in traditional hepatotoxicity testing approaches using population pooled cell sources. Here we demonstrate the use of patient-specific hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells for modeling idiosyncratic hepatotoxicity to pazopanib (PZ), a tyrosine kinase inhibitor drug associated with significant hepatotoxicity of unknown mechanistic basis...
January 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28118809/involvement-of-protoporphyrin-ix-accumulation-in-the-pathogenesis-of-isoniazid-rifampicin-induced-liver-injury-the-prevention-of-curcumin
#14
Leiyan He, Yaoxue Guo, Ye Deng, Chun Li, Chengzi Zuo, Wenxing Peng
Combination of isoniazid (INH) and rifampicin (RFP) causes liver injury frequently among tuberculosis patients. However, mechanisms of the hepatotoxicity are not entirely understood. Protoporphyrin IX (PPIX) accumulation, as an endogenous hepatotoxin, resulting from isoniazid and rifampicin co-therapy (INH/RFP) has been reported in PXR-humanized mice. Aminolevulinic acid synthase1 (ALAS1), ferrochelatase (FECH) and breast cancer resistance protein (BCRP) play crucial roles in PPIX synthesis, metabolism and transport, respectively...
February 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28073545/a-validated-uplc-ms-ms-method-for-the-surveillance-of-ten-aquatic-biotoxins-in-european-brackish-and-freshwater-systems
#15
Brett Greer, Sara E McNamee, Bas Boots, Lucia Cimarelli, Delphine Guillebault, Karim Helmi, Stefania Marcheggiani, Stefan Panaiotov, Ulrich Breitenbach, Reyhan Akçaalan, Linda K Medlin, Katrin Kittler, Christopher T Elliott, Katrina Campbell
Over the past few decades, there has been an increased frequency and duration of cyanobacterial Harmful Algal Blooms (HABs) in freshwater systems globally. These can produce secondary metabolites called cyanotoxins, many of which are hepatotoxins, raising concerns about repeated exposure through ingestion of contaminated drinking water or food or through recreational activities such as bathing/swimming. An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) multi-toxin method has been developed and validated for freshwater cyanotoxins; microcystins-LR, -YR, -RR, -LA, -LY and -LF, nodularin, cylindrospermopsin, anatoxin-a and the marine diatom toxin domoic acid...
May 2016: Harmful Algae
https://www.readbyqxmd.com/read/28073507/evidence-of-freshwater-algal-toxins-in-marine-shellfish-implications-for-human-and-aquatic-health
#16
Corinne M Gibble, Melissa B Peacock, Raphael M Kudela
The occurrence of freshwater harmful algal bloom toxins impacting the coastal ocean is an emerging threat, and the potential for invertebrate prey items to concentrate toxin and cause harm to human and wildlife consumers is not yet fully recognized. We examined toxin uptake and release in marine mussels for both particulate and dissolved phases of the hepatotoxin microcystin, produced by the freshwater cyanobacterial genus Microcystis. We also extended our experimental investigation of particulate toxin to include oysters (Crassostrea sp...
November 2016: Harmful Algae
https://www.readbyqxmd.com/read/28073477/a-review-of-the-phylogeny-ecology-and-toxin-production-of-bloom-forming-aphanizomenon-spp-and-related-species-within-the-nostocales-cyanobacteria
#17
REVIEW
Samuel Cirés, Andreas Ballot
The traditional genus Aphanizomenon comprises a group of filamentous nitrogen-fixing cyanobacteria of which several memebers are able to develop blooms and to produce toxic metabolites (cyanotoxins), including hepatotoxins (microcystins), neurotoxins (anatoxins and saxitoxins) and cytotoxins (cylindrospermopsin). This genus, representing geographically widespread and extensively studied cyanobacteria, is in fact heterogeneous and composed of at least five phylogenetically distant groups (Aphanizomenon, Anabaena/Aphanizomenon like cluster A, Cuspidothrix, Sphaerospermopsis and Chrysosporum) whose taxonomy is still under revision...
April 2016: Harmful Algae
https://www.readbyqxmd.com/read/28063643/protective-effect-of-tritone-livosone-on-oxidative-dna-damage-and-its-hepatoprotective-potential-against-various-hepatotoxic-agent-in-wistar-rats
#18
Sheetal Kashinath Medhekar, Tejas Pandurang Jadhav, Vishal Sadashiv Sasane, Vikas Suresh Shende, Nagesh Hanmantrao Aloorkar, Anjali Baburao Chincholkar, Girish Sudhakar Soman, Ajit Shankarrao Kulkarni
AIM: To evaluate antioxidant activity, DNA damage inhibition and hepatoprotecitve potential of polyherbal formulation Tritone (Livosone). METHODS: In vitro antioxidant activity of Tritone formulation was performed by using DPPH assay. Hepatoprotecitve potential of Tritone was evaluated against various hepatotoxic agents including Paracetamol (2g/kg b. wt p.o. single dose on 15th day), Galactosamine (400mg/kg b. wt. i.p. single dose on 8th day) and Alcohol (30% p...
March 2, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28062358/alterations-in-transcription-and-protein-expressions-of-hcc-related-genes-in-hepg2-cells-caused-by-microcystin-lr
#19
Xiaoyu Li, Xiangyang Zhang, Wenjie Xie, Chune Zhou, Yao Li, Xiuhua Zhang
Microcystin-LR (MC-LR) is the most common and toxic hepatotoxin and it could induce human hepatitis and hepatocellular carcinoma (HCC) via the route of drinking water. The aim of the present study was to determine the expressions of oncogenes c-fos, c-jun, c-myc, c-met, and N-ras and tumor suppressor gene PTEN in HepG2 cells following MC-LR-exposure to understand the possible mechanism of MC-LR-related human primary liver cancer. The results of qPCR and Western blotting showed that MC-LR-exposure at non- or sub-cytotoxic concentrations promoted the expressions of oncogenes c-fos, c-jun, c-myc, c-met, and N-ras while suppressed tumor-suppressor gene PTEN in HepG2 cells at both transcription and protein levels...
January 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27956256/circulating-micrornas-possible-role-as-non-invasive-diagnostic-biomarkers-in-liver-disease
#20
Kishor Pant, Senthil K Venugopal
Liver is the central organ for metabolism and the hepatocytes metabolize several drugs, hepatotoxins, alcohol, etc. Continuous exposure of the hepatocytes to these toxins result in various chronic diseases, such as alcoholic liver disease, non-alcoholic fatty liver disease, viral hepatitis and hepatocellular carcinoma. Although several diagnostic methods, such as serum markers, liver biopsy or imaging studies are currently available, most of these are either invasive or detect the disease at advanced stages...
December 9, 2016: Clinics and Research in Hepatology and Gastroenterology
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