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Krasimira Aleksandrova, Marta Stelmach-Mardas, Sabrina Schlesinger
Obesity and related metabolic disorders have become globally prevalent posing a challenge for the chronically damaged liver and predisposing the development and progression of cancer. The rising phenomenon of "obesity epidemic" may provide means for understanding why liver cancer is one of the few malignancies with rising incidence in developed countries over the last decades. Non-alcoholic fatty liver disease associated with obesity, insulin resistance, and type 2 diabetes is an increasingly recognized trigger for liver cancer in Western populations characterized by low prevalence of established risk factors for liver cancer such as viral hepatitis and hepatotoxin exposure...
2016: Recent Results in Cancer Research
Kathryn Pickup, Scott Martin, Elizabeth A Partridge, Huw B Jones, Jonathan Wills, Tim Schulz-Utermoehl, Alan McCarthy, Alison Rodrigues, Chris Page, Kerry Ratcliffe, Sunil Sarda, Ian D Wilson
The distribution, metabolism, excretion and hepatic effects of the human hepatotoxin fenclozic acid were investigated following single oral doses of 10 mg/kg to normal and bile duct-cannulated male C57BL/6J mice. Whole body autoradiography showed distribution into all tissues except the brain, with radioactivity still detectable in blood, kidney and liver at 72 h post-dose. Mice dosed with [(14)C]-fenclozic acid showed acute centrilobular hepatocellular necrosis, but no other regions of the liver were affected...
November 28, 2016: Archives of Toxicology
Shamantha Reddy, Pragnyadipta Mishra, Sana Qureshi, Singh Nair, Tracey Straker
Many conventional drugs used today, including isoniazid, dapsone, and acetaminophen, are well recognized culprits of hepatotoxicity. With increasing use of complementary and alternative medical therapies, several herbal medicines, such as Ma-Huang, kava, and chaparral leaf, have been implicated as hepatotoxins. Hepatotoxicity may be the most frequent adverse reaction to these herbal remedies when taken in excessive quantities. A myriad of liver dysfunctions may occur including transient liver enzyme abnormalities due to acute and chronic hepatitis...
December 2016: Journal of Clinical Anesthesia
Mayuko Ichimura, Miki Masuzumi, Miku Kawase, Mika Sakaki, Shizuka Tamaru, Yasuo Nagata, Kazunari Tanaka, Kazuhito Suruga, Koichi Tsuneyama, Satoru Matsuda, Katsuhisa Omagari
Certain modified diets containing saturated fatty acids, cholesterol or fructose lead to the development of nonalcoholic steatohepatitis (NASH)-related fibrosis in rodents; however, progression to cirrhosis is rare. Experimental liver cirrhosis models have relied on genetic manipulation or administration of hepatotoxins. This study aimed to establish a reliable dietary model of NASH-related cirrhosis in a relatively short period. Male Sprague-Dawley rats (9 weeks of age) were randomly assigned to normal, high-fat (HF), or two types (1...
October 24, 2016: Journal of Nutritional Biochemistry
Lawrence A Vernetti, Andreas Vogt, Albert Gough, D Lansing Taylor
In this article, we review the past applications of in vitro models in identifying human hepatotoxins and then focus on the use of multiscale experimental models in drug development, including the use of zebrafish and human cell-based, 3-dimensional, microfluidic systems of liver functions as key components in applying Quantitative Systems Pharmacology (QSP). We have implemented QSP as a platform to improve the rate of success in the process of drug discovery and development of therapeutics.
February 2017: Clinics in Liver Disease
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
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