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https://www.readbyqxmd.com/read/28069987/transgenic-zebrafish-reporter-lines-as-alternative-in-vivo-organ-toxicity-models
#1
Kar Lai Poon, Xingang Wang, Serene Gp Lee, Ashley S Ng, Wei Huang Goh, Zhonghua Zhao, Muthafar Al-Haddawi, Haishan Wang, Sinnakaruppan Mathavan, Phillip W Ingham, Claudia Mcginnis, Tom J Carney
Organ toxicity, particularly liver toxicity, remains one of the major reasons for termination of drug candidates in the development pipeline as well as withdrawal or restrictions of marketed drugs. A screening-amenable alternative in vivo model such as zebrafish would therefore find immediate application in the early prediction of unacceptable organ toxicity. To identify highly upregulated genes as biomarkers of toxic responses in the zebrafish model, a set of well-characterized reference drugs that cause drug induced liver injury (DILI) in the clinic were applied to zebrafish larvae and adults...
January 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28050235/primary-liver-injury-and-delayed-resolution-of-liver-stiffness-after-alcohol-detoxification-in-heavy-drinkers-with-the-pnpla3-variant-i148m
#2
Vanessa Rausch, Teresa Peccerella, Carolin Lackner, Eray Yagmur, Helmut-Karl Seitz, Thomas Longerich, Sebastian Mueller
AIM: To investigate the influence of PNPLA3 genotype in heavy drinkers on serum markers and liver stiffness (LS) during alcohol withdrawal and its association with histology. METHODS: Caucasian heavy drinkers (n = 521) with a mean alcohol consumption of 192.1 g/d (median alcohol consumption: 169.0 g/d; 95%CI: 179.0-203.3) were enrolled at the Salem Medical Center, University of Heidelberg. LS was measured by transient elastography (Fibroscan, Echosens SA, Paris, France)...
December 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/28031015/melatonin-pharmacology-functions-and-therapeutic-benefits
#3
Sylvie Tordjman, Sylvie Chokron, Richard Delorme, Annaëlle Charrier, Eric Bellissant, Nemat Jaafari, Claire Fougerou
Melatonin synchronizes central but also peripheral oscillators (fetal adrenal gland, pancreas, liver, kidney, heart, lung, fat, gut, etc.), allowing temporal organization of biological functions through circadian rhythms in relation to periodic environmental changes and therefore adaptation of the individual to his/her internal and external environment. Measures of melatonin are considered the best peripheral indices of human circadian timing. First, the pharmacology of melatonin (biosynthesis and circadian rhythms, pharmacokinetics and mechanisms of action) is described, allowing a better understanding of the short and long term effects of melatonin following its immediate or prolonged release...
December 28, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/28026023/effects-of-long-term-ethanol-consumption-and-aldh1b1-depletion-on-intestinal-tumourigenesis-in-mice
#4
Mike F Müller, Ying Zhou, David J Adams, Mark J Arends
Ethanol and its metabolite acetaldehyde have been classified as carcinogens for the upper aerodigestive tract, liver, breast and colorectum. Whereas mechanisms related to oxidative stress and Cyp2e1 induction seem to prevail in the liver, and acetaldehyde has been proposed to play a crucial role in the upper aerodigestive tract, pathological mechanisms in the colorectum have not yet been clarified. Moreover, all evidence for a pro-carcinogenic role of ethanol in colorectal cancer is derived from correlations observed in epidemiological studies or from rodent studies with additional carcinogen application or tumour suppressor gene inactivation...
December 27, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27996102/current-sights-for-mechanisms-of-deoxynivalenol-induced-hepatotoxicity-and-prospective-views-for-future-scientific-research-a-mini-review
#5
REVIEW
Zhao Peng, Liangkai Chen, Andreas K Nüssler, Liegang Liu, Wei Yang
Deoxynivalenol (DON) belongs to the group B trichothecenes, which are the most common mycotoxins in cereal commodities. It is very stable within the temperature range 170-350 °C, showing no reduction in its concentration after 30 min at 170 °C. This chemical property is a very dangerous factor for human and animal health. Liver is also responsible for the detoxification and formation of DON-glucuronide in both human and animals. Some studies already demonstrated that DON could induce liver damage remarkably through DON altering expressions of p53, caspase-3, caspase-7, caspase-8 and Bax in different cell lines...
December 20, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27993722/use-of-polymer-conjugates-for-the-intraperoxisomal-delivery-of-engineered-human-alanine-glyoxylate-aminotransferase-as-a-protein-therapy-for-primary-hyperoxaluria-type-i
#6
Alessandro Roncador, Elisa Oppici, Marina Talelli, Amaya Niño Pariente, Marta Donini, Stefano Dusi, Carla Borri Voltattorni, María J Vicent, Barbara Cellini
Alanine:glyoxylate aminotransferase (AGT) is a liver peroxisomal enzyme whose deficit causes the rare disorder Primary Hyperoxaluria Type I (PH1). We now describe the conjugation of poly(ethylene glycol)-co-poly(L-glutamic acid) (PEG-PGA) block-co-polymer to AGT via the formation of disulfide bonds between the polymer and solvent-exposed cysteine residues of the enzyme. PEG-PGA conjugation did not affect AGT structural/functional properties and allowed the enzyme to be internalized in a cellular model of PH1 and to restore glyoxylate-detoxification...
December 18, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27979702/quercetin-and-baicalein-suppress-monocrotaline-induced-hepatic-sinusoidal-obstruction-syndrome-in-rats
#7
Jiaqi Zhang, Yuchen Sheng, Liang Shi, Zhiyong Zheng, Minwei Chen, Bin Lu, Lili Ji
Hepatic sinusoidal obstruction syndrome (SOS) is a rare liver disease with considerable mortality. This study is designed to observe the protection of quercetin and baicalein against monocrotaline (MCT)-induced SOS in rats and its engaged mechanism. Rats were pre-administrated with MCT (90mg/kg) to induce SOS, and 6, 30h later were orally given with quercetin and baicalein (40mg/kg) twice. Results of detecting rats with liver ascites, measuring serum transaminases, total bilirubin (TBil) and bile acids (TBA), analyzing blood cells, liver histological evaluation and scanning electron microscope observation all demonstrated the detoxification of quercetin and baicalein against MCT-induced SOS in rats...
December 13, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27960020/-the-hyperoxalurias
#8
Martino Marangella, Michele Petrarulo, Francesca Bermond, Cristina Marcuccio, Corrado Vitale
Oxalate (Ox) is an end-product of metabolism, important for poor solubility of its calcium salt in biological fluids. Ox can therefore be found in about 70% of urinary calculi. Hyperoxaluria (HOx) defined as Ox exceeding 0.5 mmol)/day, may cause nephrolithiasis/nephrocalcinosis and may be classified as dietary (DH), enteric (EH) or primary (PH). Fractional intestinal absorption of Ox is less than 10%, but increases to over 20% at calcium intakes below 200 mg/day. DH is often related to low-calcium diets. EH is caused by non-absorbed fatty acids which bind to calcium and lower its concentration in the intestinal lumen...
2016: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/27957242/performance-of-cold-preserved-rat-liver-microorgans-as-the-biological-component-of-a-simplified-prototype-model-of-bioartificial-liver
#9
María Dolores Pizarro, María Gabriela Mediavilla, Alejandra Beatriz Quintana, Ángel Luis Scandizzi, Joaquín Valentín Rodriguez, María Eugenia Mamprin
AIM: To develop a simplified bioartificial liver (BAL) device prototype, suitable to use freshly and preserved liver Microorgans (LMOs) as biological component. METHODS: The system consists of 140 capillary fibers through which goat blood is pumped. The evolution of hematocrit, plasma and extra-fiber fluid osmolality was evaluated without any biological component, to characterize the prototype. LMOs were cut and cold stored 48 h in BG35 and ViaSpan(®) solutions...
November 28, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27955686/nutrigenomic-effects-of-glucosinolates-on-liver-muscle-and-distal-kidney-in-parasite-free-and-salmon-louse-infected-atlantic-salmon
#10
Stanko Skugor, Helle Jodaa Holm, Anne Kari Bjelland, Jorge Pino, Øystein Evensen, Aleksei Krasnov, Simon Wadsworth
BACKGROUND: Reduction of Lepeophtheirus salmonis infection in Atlantic salmon achieved by glucosinolates (GLs) from Brassica plants was recently reported. However, wider application of functional feeds based on GLs requires better knowledge of their positive and adverse effects. METHODS: Liver, distal kidney and muscle transcriptomes of salmon exposed to the extreme dose of GLs were profiled by microarray, while qPCR analysis followed up selected hepatic and renal responses under the extreme and moderate GLs dose during the L...
December 12, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27951519/differential-cytokine-levels-between-early-withdrawal-and-remission-states-in-patients-with-alcohol-dependence
#11
Che-Hung Yen, Pei-Shen Ho, Yi-Wei Yeh, Chih-Sung Liang, Shin-Chang Kuo, Chang-Chih Huang, Chun-Yen Chen, Mei-Chen Shih, Kuo-Hsing Ma, Yueh-Feng Sung, Ru-Band Lu, San-Yuan Huang
Alcohol dependence (AD) leads to altered innate and adaptive immune responses, and frequently co-occurs with inflammation. Therefore, inflammatory cytokines potentially play a crucial role in the development of alcohol-related illnesses. This study evaluated changes in plasma cytokine concentrations, liver function, cravings, depression severity, and cognitive function in male patients with AD, during the course of an alcohol-detoxification program. A total of 78 male patients with AD were recruited for a conservative detoxification program; and cytokine levels, depressive score, and cognitive impairment applying the Trail Making Test (TMT) were evaluated during early withdrawal (baseline) and after 4 weeks of abstinence from alcohol...
October 20, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27940000/impact-of-dietary-phytol-on-lipid-metabolism-in-scp2-scpx-l-fabp-null-mice
#12
Sherrelle Milligan, Gregory G Martin, Danilo Landrock, Avery L McIntosh, John T Mackie, Friedhelm Schroeder, Ann B Kier
In vitro studies suggest that liver fatty acid binding protein (L-FABP) and sterol carrier protein-2/sterol carrier protein-x (SCP2/SCPx) gene products facilitate uptake and metabolism and detoxification of dietary-derived phytol in mammals. However, concomitant upregulation of L-FABP in SCP2/SCPx null mice complicates interpretation of their physiological phenotype. Therefore, the impact of ablating both the L-FABP gene and SCP2/SCPx gene (L-FABP/SCP2/SCPx null or TKO) was examined in phytol-fed female wild-type (WT) and TKO mice...
December 6, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27923802/xanthohumol-prevents-dna-damage-by-dietary-carcinogens-results-of-a-human-intervention-trial
#13
Christoph Pichler, Franziska Ferk, Halh Al-Serori, Wolfgang Huber, Walter Jäger, Monika Waldherr, Miroslav Mišík, Michael Kundi, Armen Nersesyan, Irene Herbacek, Siegfried Knasmueller
Xanthohumol (XN) is a hop flavonoid contained in beers and soft drinks. In vitro and animal studies indicated that XN has DNA and cancer protective properties. To find out if it causes DNA protective effects in humans, an intervention trial was conducted in which the participants (n = 22) consumed a XN containing drink (12 mg XN/P/d). We monitored prevention of DNA damage induced by representatives of major groups of dietary carcinogens [i.e., nitrosodimethylamine (NDMA) benzo(a)pyrene (B(a)P) and the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)]...
December 6, 2016: Cancer Prevention Research
https://www.readbyqxmd.com/read/27920621/toxins-toxicity-and-endotoxemia-a-historical-and-clinical-perspective-for-chiropractors
#14
REVIEW
David R Seaman
OBJECTIVE: The purpose of this commentary is to review the notion of toxicity in the context of chiropractic practice. DISCUSSION: The belief that body toxicity is the cause of disease has been promoted for thousands of years. Prior to the emergence of the chiropractic profession, the medical profession embraced the notion that the body becomes "toxic," requiring detoxification interventions or surgery. The legacy of body toxicity within the chiropractic approach to patient care began with Daniel David Palmer...
December 2016: Journal of Chiropractic Humanities
https://www.readbyqxmd.com/read/27913847/patulin-transformation-products-and-last-intermediates-in-its-biosynthetic-pathway-e-and-z-ascladiol-are-not-toxic-to-human-cells
#15
Joanna Tannous, Selma P Snini, Rhoda El Khoury, Cécile Canlet, Philippe Pinton, Yannick Lippi, Imourana Alassane-Kpembi, Thierry Gauthier, André El Khoury, Ali Atoui, Ting Zhou, Roger Lteif, Isabelle P Oswald, Olivier Puel
Patulin is the main mycotoxin contaminating apples. During the brewing of alcoholic beverages, this mycotoxin is degraded to ascladiol, which is also the last precursor of patulin. The present study aims (1) to characterize the last step of the patulin biosynthetic pathway and (2) to describe the toxicity of ascladiol. A patE deletion mutant was generated in Penicillium expansum. In contrast to the wild strain, this mutant does not produce patulin but accumulates high levels of E-ascladiol with few traces of Z-ascladiol...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27910771/induction-of-flavin-containing-monooxygenase-in-mice-by-oral-administration-of-phellinus-baumii-agaricomycetes-extract
#16
Batbayar Sainkhuu, Beom Su Park, Ha Won Kim
Phellinus baumii is a yellow mushroom long used in alternative medicine in Korea and other central Asian countries. To identify genes affected by a single or 7-day oral administration of a water extract of Ph. Baumii, mouse liver tissue was analyzed using microarrays. The results showed that 8 and 23 genes were upregulated and 3 and 11 genes downregulated more than 3-fold by single and multiple oral administrations of 100 mg/kg PBE, respectively. Among the upregulated genes, the expression of 3 flavin-containing monooxygenase (Fmo) family genes, Fmo2-4, was upregulated in a concentration-dependent manner...
2016: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/27907862/alteration-of-%C3%AE-n-acetylgalactosaminidase-nagalase-concentration-in-alcohol-dependent-individuals-without-liver-disease-during-the-detoxification-therapy
#17
Margarita Zoga, Thomas Nikou, Anastasios Ioannidis, Elias Tzavellas, Thomas Paparrigopoulos, Konstantinos Th Lambrokostopoulos, Vassilis G Vasdekis, Maria Magana, Stylianos Chatzipanagiotou
BACKGROUND: The present study aimed to investigate for the first time, the alteration of α-N-acetylgalactosaminidase (nagalase) concentration in alcohol-dependent individuals without liver disease, before, during and at the end of the detoxification therapy. METHODS: Forty-eight alcohol-dependent individuals without liver disease who were admitted for alcohol detoxification, and eighty-four healthy controls participated in this study. Patients' blood was obtained upon admission, two weeks later and after the completion of the detoxification period (4-5 weeks)...
January 1, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/27905861/sodium-bisulfite-pyrosequencing-revealed-that-developmental-exposure-to-environmental-contaminant-mixtures-does-not-affect-dna-methylation-of-dna-repeats-in-sprague-dawley-rats
#18
Daniel Desaulniers, Cathy Cummings-Lorbetskie, Nanqin Li, Gong-Hua Xiao, Leonora Marro, Nasrin Khan, Karen Leingartner
Hypomethylation of DNA repeats has been linked to diseases and cancer predisposition. Human studies suggest that higher blood concentrations of environmental contaminants (EC) correlate with levels of hypomethylation of DNA repeats in blood. The objective of this study was to examine the effect of in utero and/or lactational exposure to EC on the methylation of DNA repeats (LINE-1 and identifier element) in Sprague-Dawley rat pups at birth, at postnatal day (PND) 21, and in adulthood (PND78-86). From gestation day 0 to PND20, dams were exposed to a mixture "M" of polychlorinated biphenyls (PCB), pesticides, and methylmercury (MeHg), at 0...
December 1, 2016: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/27904813/glycyrrhetinic-acid-might-increase-the-nephrotoxicity-of-bakuchiol-by-inhibiting-cytochrome-p450-isoenzymes
#19
Aifang Li, Nana Ma, Zijing Zhao, Mei Yuan, Hua Li, Qi Wang
BACKGROUND: Licorice, a popular traditional Chinese medicine (TCM), is widely used to moderate the effects (detoxification) of other herbs in TCM and often combined with Fructus Psoraleae. However, the classical TCM book states that Fructus Psoraleae is incompatible with licorice; the mechanism underlying this incompatibility has not been identified. Glycyrrhetinic acid (GA), the active metabolite of licorice, may increase the toxicity of bakuchiol (BAK), the main chemical ingredient in Psoralea corylifolia, by inhibiting its detoxification enzymes CYP450s...
2016: PeerJ
https://www.readbyqxmd.com/read/27901316/small-subcompartmentalized-microreactors-as-support-for-hepatocytes
#20
Yan Zhang, Marie Baekgaard-Laursen, Brigitte Städler
Mimicking specific structural or functional aspects of cells is considered a promising approach to substitute for missing or lost cellular functions. However, the interaction of such artificial assemblies with their biological counterparts including the exploitation of the activity of the synthetic partner remains thus-far a rather unexplored avenue. Herein, the assembly of active microreactors with similar size to hepatocytes is reported. These microreactors are successfully cocultured with hepatocytes into bionic tissue for up to 10 d...
November 30, 2016: Advanced Healthcare Materials
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