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Harriet Gaskell, Parveen Sharma, Helen E Colley, Craig Murdoch, Dominic P Williams, Steven D Webb
More predictive in vitro liver models are a critical requirement for preclinical screening of compounds demonstrating hepatotoxic liability. 3D liver spheroids have been shown to have an enhanced functional lifespan compared to 2D monocultures; however a detailed characterisation of spatiotemporal function and structure of spheroids still needs further attention before widespread use in industry. We have developed and characterized the structure and function of a 3D liver spheroid model formed from C3A hepatoma cells...
June 1, 2016: Toxicology Research
Xi-Dong Li, Bing-Hua Qiu, Fang-Cheng Su, Shao-Xia Sun
: No previous study has reported the association between nonalcoholic fatty liver disease (NAFLD) and the risk of hypertension in the Chinese population. Therefore, the aim of this study was to evaluate the relationship between NAFLD and hypertension in a middle-aged Chinese population. The study subject was (a group of) 1006 Chinese adults aged 45-60 y in Shandong Province who participated in the Weifang Nutrition and Health Survey (2014-2015). Hypertension was defined as systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥ 9 0mmHg...
2016: Clinical and Experimental Hypertension: CHE
Lucillia R de O Torres, Fernanda C de Santana, Francisco L Torres-Leal, Illana L P de Melo, Luciana T Yoshime, Emidio M Matos-Neto, Marília C L Seelaender, Cintia M M Araújo, Bruno Cogliati, Jorge Mancini-Filho
Carbon tetrachloride (CCl4) is a potent hepatotoxin, capable of generating free radicals that lead to oxidative stress and the inflammation process. Pequi almond oil (PAO) has been reported to possess unsaturated fatty acid and antioxidant compounds related to beneficial effects on oxidation and inflammatory conditions. The present study was undertaken to evaluate the hepatoprotective effects of handmade and coldpressed PAO on CCl4-induced acute liver injury. The possible mechanisms underlying the effect on liver injury enzymes, histopathological parameters, lipid profile, lipid peroxidation, and antioxidant and detoxification defense systems, as well as inflammatory parameters, were determined...
September 10, 2016: Food and Chemical Toxicology
Eddie T T Tan, Rafat Al Jassim, Bruce R D'Arcy, Mary T Fletcher
Camel meat production for human consumption and pet food manufacture accounts for a relatively small part of overall red meat production in Australia. Reliable statistical data for the Australian production and consumption of camel meat are not available; however, it is estimated that 300,000 feral camels roam within the desert of central Australia, with an annual usage of more than 3000 camels for human consumption, 2000 for pet food manufacture and a smaller number for live export. Despite a small Australian camel meat production level, the usage of camel meat for pet food has been restricted in recent years due to reports of serious liver disease and death in dogs consuming camel meat...
October 2016: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
Valentina Peta, Djamel Elaribi, Ludovico Abenavoli
Alcohol is considered one of the most common hepatotoxin, and chronic alcoholic liver disease is affecting millions of subjects worldwide. The three most frequently manifestations of alcoholic liver disease are steatosis, acute alcoholic hepatitis and liver cirrhosis. The diagnosis of Alcoholic Liver Diseases (ALD) is made by clinical and laboratory analysis. Actually do not exist a single laboratory test able to confirm the diagnosis of ALD, but in the last years several serum markers and laboratory abnormalities have been discovered in these patients...
2016: Reviews on Recent Clinical Trials
Eddie T T Tan, Christopher M Materne, Richard G Silcock, Bruce R D'Arcy, Rafat Al Jassim, Mary T Fletcher
Livestock industries have maintained a keen interest in pasture legumes because of the high protein content and nutritive value. Leguminous Indigofera plant species have been considered as having high feeding values to be utilized as pasture, but the occurrence of the toxic constituent indospicine in some species has restricted this utility. Indospicine has caused both primary and secondary hepatotoxicosis and also reproductive losses, but has only previously been determined in a small number of Indigofera species...
August 31, 2016: Journal of Agricultural and Food Chemistry
Ramanathan Raghu, Sivanesan Karthikeyan
HIV/AIDS patients are more prone for opportunistic TB infections and they are administered the combined regimen of anti-retroviral drug zidovudine (AZT) and isoniazid (INH) for therapy. However, AZT+INH treatment has been documented to induce injury and remedial measures to prevent this adversity are not clearly defined. Silibinin (SBN) is a natural hepatoprotective principle isolated from medicinal plant Silybum marianum and is currently used for therapy of various liver diseases. This study investigate the hepatotoxic potentials of AZT alone, INH alone and AZT+INH treatments and the mitigating potentials of SBN against these drugs induced toxic insults of liver in rats...
September 2016: Environmental Toxicology and Pharmacology
Eddie T T Tan, Rafat Al Jassim, A Judy Cawdell-Smith, Selina M Ossedryver, Bruce R D'Arcy, Mary T Fletcher
Indospicine (l-2-amino-6-amidinohexanoic acid) is a natural hepatotoxin found in all parts of some Indigofera plants such as Indigofera linnaei and Indigofera spicata. Several studies have documented a susceptibility to this hepatotoxin in different species of animals, including cattle, sheep, dogs, and rats, which are associated with mild to severe liver disease after prolonged ingestion. However, there is little published data on the effects of this hepatotoxin in camels, even though Indigofera plants are known to be palatable to camels in central Australia...
August 31, 2016: Journal of Agricultural and Food Chemistry
Anna C Y Yeung, Paul M D'Agostino, Anne Poljak, James McDonald, Mark W Bligh, T David Waite, Brett A Neilan
UNLABELLED: The hepatotoxin microcystin (MCYST) is produced by a variety of freshwater cyanobacterial species, including Microcystis aeruginosa Interestingly, MCYST-producing M. aeruginosa strains have been shown to outcompete their nontoxic counterparts under iron-limiting conditions. However, the reasons for this are unclear. Here we examined the proteomic response of M. aeruginosa PCC 7806 continuous cultures under different iron and growth regimes. Iron limitation was correlated with a global reduction in levels of proteins associated with energy metabolism and photosynthesis...
October 1, 2016: Applied and Environmental Microbiology
Kimberly M Parker, Elke S Reichwaldt, Anas Ghadouani, William A Mitch
The transport of microcystin, a hepatotoxin produced by cyanobacteria (e.g., Microcystis aeruginosa), to estuaries can adversely affect estuarine and coastal ecosystems. We evaluated whether halogen radicals (i.e., reactive halogen species (RHS)) could significantly contribute to microcystin photodegradation during transport within estuaries. Experiments in synthetic and natural water samples demonstrated that the presence of seawater halides increased quantum yields for microcystin indirect photodegradation by factors of 3-6...
August 16, 2016: Environmental Science & Technology
Erik Borchert, Stephen A Jackson, Fergal O'Gara, Alan D W Dobson
Three different deep sea sponge species, Inflatella pellicula, Poecillastra compressa, and Stelletta normani comprising seven individual samples, retrieved from depths of 760-2900 m below sea level, were investigated using 454 pyrosequencing for their secondary metabolomic potential targeting adenylation domain and ketosynthase domain sequences. The data obtained suggest a diverse microbial origin of nonribosomal peptide synthetases and polyketide synthase fragments that in part correlates with their respective microbial community structures that were previously described and reveals an untapped source of potential novelty...
2016: Frontiers in Microbiology
Simona Clichici, Diana Olteanu, Adriana Filip, Andras-Laszlo Nagy, Adrian Oros, Petru A Mircea
Silymarin (Si) is a herbal product with hepatoprotective potential, well-known for its antioxidant, anti-inflammatory, and immunomodulatory properties. We have recently demonstrated that the usual therapeutic doses of Si are capable of inhibiting the progression of incipient liver fibrosis. We aimed at further investigating the benefits of Si administration upon liver alterations after the hepatotoxin discontinuation, using CCl4 to induce liver injuries on rats. CCl4 administration induces first of all oxidative stress, but other mechanisms, such as inflammation and liver fibrosis are also triggered...
August 2016: Journal of Medicinal Food
Madhav Sachar, Feng Li, Ke Liu, Pengcheng Wang, Jie Lu, Xiaochao Ma
Isoniazid (INH) can cause hepatotoxicity. In addition, INH is contraindicated in patients suffering from porphyrias. Our metabolomic analysis revealed that chronic treatment with INH in mice causes a hepatic accumulation of protoporphyrin IX (PPIX). PPIX is an intermediate in the heme biosynthesis pathway, and it is also known as a hepatotoxin. We further found that INH induces delta-aminolevulinate synthase 1 (ALAS1), the rate-limiting enzyme in heme biosynthesis. We also found that INH downregulates ferrochelatase (FECH), the enzyme that converts PPIX to heme...
August 15, 2016: Chemical Research in Toxicology
D F Niedrig, G Bucklar, M Fetzer, S Mächler, C Gött, S Russmann
WHAT IS KNOWN AND OBJECTIVES: Paracetamol is a frequently used antipyretic and analgesic drug, but also a dose-dependent hepatotoxin. Unintentional paracetamol overdosing is a common medication error in hospitals. The present study aimed at (i) analysis of unintentional paracetamol overdosing in hospitalized patients; (ii) development, implementation and outcome analysis of an alert algorithm for the prevention of relevant paracetamol overdosing. METHODS: All patients who received paracetamol in a Swiss tertiary care hospital during 2011 to 2014 were analysed to detect cases of paracetamol overdosing in a local pharmacoepidemiological database...
October 2016: Journal of Clinical Pharmacy and Therapeutics
Pia I Scherer, Uta Raeder, Juergen Geist, Katrin Zwirglmaier
Cyanobacteria, such as the toxin producer Microcystis aeruginosa, are predicted to be favored by global warming both directly, through elevated water temperatures, and indirectly, through factors such as prolonged stratification of waterbodies. M. aeruginosa is able to produce the hepatotoxin microcystin, which causes great concern in freshwater management worldwide. However, little is known about the expression of microcystin synthesis genes in response to climate change-related factors. In this study, a new RT-qPCR assay employing four reference genes (GAPDH, gltA, rpoC1, and rpoD) was developed to assess the expression of two target genes (the microcystin synthesis genes mcyB and mcyD)...
July 14, 2016: MicrobiologyOpen
Séverine Le Manach, Nour Khenfech, Hélène Huet, Qin Qiao, Charlotte Duval, Arul Marie, Gérard Bolbach, Gilles Clodic, Chakib Djediat, Cécile Bernard, Marc Edery, Benjamin Marie
Cyanobacterial blooms often occur in freshwater lakes and constitute a potential health risk to human populations, as well as to other organisms. However, their overall and specific implications for the health of aquatic organisms that are chronically and environmentally exposed to cyanobacteria producing hepatotoxins, such as microcystins (MCs), together with other bioactive compounds have still not been clearly established and remain difficult to assess. The medaka fish was chosen as the experimental aquatic model for studying the cellular and molecular toxicological effects on the liver after chronic exposures (28 days) to environmentally relevant concentrations of pure MC-LR, complex extracts of MC producing or nonproducing cyanobacterial biomasses, and of a Microcystis aeruginosa natural bloom...
August 2, 2016: Environmental Science & Technology
Kang Ho Kim, Jae Man Lee, Ying Zhou, Sanjiv Harpavat, David D Moore
Liver fibrosis is a reversible wound-healing process that is protective in the short term, but prolonged fibrotic responses lead to excessive accumulation of extracellular matrix components that suppresses hepatocyte regeneration, resulting in permanent liver damage. Upon liver damage, nonparenchymal cells including immune cells and hepatic stellate cells (HSCs) have crucial roles in the progression and regression of liver fibrosis. Here, we report differential roles of the glucocorticoid receptor (GR), acting in immune cells and HSCs, in liver fibrosis...
August 2016: Molecular Endocrinology
Xinran Zhang, Jing Li, Jer-Yen Yang, Karl V Wood, Arlene P Rothwell, Weiguang Li, Ernest R Blatchley Iii
Microcystin-LR (MC-LR) is a potent hepatotoxin that is often associated with blooms of cyanobacteria. Experiments were conducted to evaluate the efficiency of the chlorine/UV process for MC-LR decomposition and detoxification. Chlorinated MC-LR was observed to be more photoactive than MC-LR. LC/MS analyses confirmed that the arginine moiety represented an important reaction site within the MC-LR molecule for conditions of chlorination below the chlorine demand of the molecule. Prechlorination activated MC-LR toward UV254 exposure by increasing the product of the molar absorption coefficient and the quantum yield of chloro-MC-LR, relative to the unchlorinated molecule...
July 19, 2016: Environmental Science & Technology
Huijuan Yang, Rui Dai, Huiyan Zhang, Chenglong Li, Xiya Zhang, Jianzhong Shen, Kai Wen, Zhanhui Wang
Microcystins (MCs) and nodularin (NOD) are cyanobacterial hepatotoxins that can greatly harm human health. Multi-analyte immunoassays provide efficient and cheap methods of screening these toxins. To develop a multi-analyte immunoassay, an antibody with both broad specificity and high affinity for structurally similar algal toxins is urgently needed. In this study, microcystin-leucine-arginine (MC-LR) and NOD were conjugated to carrier proteins using a one-step active ester (AE) method and multistep thiol-ene click chemistry and glutaraldehyde method, respectively...
September 2016: Analytical and Bioanalytical Chemistry
Rafael Vicentini Popin, Janaina Rigonato, Vinicius Augusto Carvalho Abreu, Ana Paula Dini Andreote, Savênia Bonoto Silveira, Clarisse Odebrecht, Marli Fatima Fiore
We report here the draft genome assembly of the brackish cyanobacterium Nodularia spumigena strain CENA596 isolated from a shrimp production pond in Rio Grande do Sul, Brazil. The draft genome consists of 291 contigs with a total size of 5,189,679 bp. Secondary metabolite annotations resulted in several predicted gene clusters, including those responsible for encoding the hepatotoxin nodularin.
2016: Genome Announcements
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