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liver detoxification

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https://www.readbyqxmd.com/read/28428138/pregnane-x-receptor-regulates-the-ahr-cyp1a1-pathway-and-protects-liver-cells-from-benzo-%C3%AE-pyrene-induced-dna-damage
#1
Hongmei Cui, Xinsheng Gu, Jingshu Chen, Ying Xie, Sui Ke, Jing Wu, Andrei Golovko, Benjamin Morpurgo, Chunhong Yan, Timothy D Phillips, Wen Xie, Jianyuan Luo, Zhijun Zhou, Yanan Tian
Pregnane X receptor (PXR) plays an important role in protecting cells from mutagenic DNA damages induced by endogenous and exogenous toxicants. This protective function is often attributed to the PXR-regulated metabolic detoxification. Here we report a novel potential mechanism that PXR reduces benzo-[α]-pyrene(BaP)-induced DNA damage through inhibiting the transcriptional activity of aryl hydrocarbon receptor (AhR) which plays a pivotal role in the bioactivation of BaP. We have utilized three well-characterized cell lines, i...
April 17, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28417197/origin-function-and-fate-of-metallothionein-in-human-blood
#2
Mohammad Tariqur Rahman, Nazmul Haque, Noor Hayaty Abu Kasim, Marc De Ley
Toxic heavy metals, toxic organic compounds, reactive oxygen species (ROS), infections, and temperature are well-known metallothionein (MT) inducers in human blood. The current review aims to summarize synthesis, function, and fate of human blood MT in response to the known MT inducers. Part of the MTs that are synthesized in different organs such as the liver, kidney, and spleen is transported and stored in different blood cells and in plasma. Cells of the circulatory system also synthesize MT. From the circulation, MT returns to the kidney where the metal-bound MTs are degraded to release the metal ion that in turn induces MT expression therein...
April 18, 2017: Reviews of Physiology, Biochemistry and Pharmacology
https://www.readbyqxmd.com/read/28414161/metabolism-of-okadaic-acid-by-nadph-dependent-enzymes-present-in-human-or-rat-liver-s9-fractions-results-in-different-toxic-effects
#3
Franziska Kolrep, Kathleen Rein, Alfonso Lampen, Stefanie Hessel
The lipophilic marine biotoxin okadaic acid (OA) represents a natural contaminant produced by algae accumulating in seafood. Acute intoxications result in diarrhetic shellfish poisoning causing symptoms like nausea, vomiting and abdominal cramps. OA was preincubated with liver enzymes present in S9 fractions from humans, rats and rats pretreated with enzyme inducers in the presence or absence of the cofactor NADPH to investigate hepatic metabolism. Cytotoxicity was examined in HepG2 cells and metabolites of OA were determined by LC-MS/MS...
April 14, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28414139/ligand-dependent-and-independent-regulation-of-human-hepatic-sphingomyelin-phosphodiesterase-acid-like-3a-expression-by-pregnane-x-receptor-and-crosstalk-with-liver-x-receptor
#4
Judith Jeske, Andreas Bitter, Wolfgang E Thasler, Thomas S Weiss, Matthias Schwab, Oliver Burk
Pregnane X receptor (PXR) mainly regulates xenobiotic metabolism and detoxification. Additionally, it exerts pleiotropic effects on liver physiology, which in large parts depend on transrepression of other liver-enriched transcription factors. Based on the hypothesis that lower expression levels of PXR may reduce the extent of this inhibition, an exploratory genome-wide transcriptomic profiling was performed using HepG2 cell clones with different expression levels of PXR. This screen and confirmatory real-time RT-PCR identified sphingomyelin phosphodiesterase acid-like (SMPDL) 3A, a novel nucleotide phosphodiesterase and phosphoramidase, as being up-regulated by PXR-deficiency...
April 13, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28412453/in-vitro-mercaptopyruvate-sulfurtransferase-species-comparison-in-humans-and-common-laboratory-animals
#5
Bryant M Moeller, Daune L Crankshaw, Jacquie Briggs, Herbert Nagasawa, Steven E Patterson
Cyanide is a metabolic poison that inhibits cytochrome c oxidase. Its broad applications in manufacturing and history as an agent of warfare/terror highlight the limitations in approved cyanide antidotes for mass casualties. Sulfanegen, a pre-clinical antidote for cyanide poisoning, exploits an endogenous detoxification pathway and should be amenable to mass-casualty scenarios. Because human studies are unethical, determination of appropriate animal species as models in translational studies for FDA approval under the "Animal Rule" are critical...
April 12, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28410323/effect-of-continuous-renal-replacement-therapy-on-outcome-in-pediatric-acute-liver-failure-is-the-clearance-mechanism-appropriate-for-detoxification
#6
Puneet Jain, Ramachandran Rameshkumar, Ponnarmeni Satheesh, Subramanian Mahadevan
No abstract text is available yet for this article.
May 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28397506/-coffee-in-cancer-chemoprevention
#7
J Neuwirthová, B Gál, P Smilek, P Urbánková
Coffee consumption is associated with a reduced risk of several diseases including cancer. Its chemopreventive effect has been studied in vitro, in animal models, and more recently in humans. Several modes of action have been proposed, namely, inhibition of oxidative stress and damage, activation of metabolizing liver enzymes involved in carcinogen detoxification processes, and anti-inflammatory effects. The antioxidant activity of coffee relies partly on its chlorogenic acid content and is increased during the roasting process...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28395205/induction-of-erod-and-bfcod-activities-in-tissues-of-barbel-barbus-callensis-from-a-water-reservoir-in-algeria
#8
Safia Habila, Essaid Leghouchi, Ana Valdehita, Azucena Bermejo-Nogales, Smail Khelili, José M Navas
EROD and BFCOD activities were measured in liver and gills of barbel (Barbus callensis, a native North African species) captured at Beni Haroun lake, the most important water reservoir in Algeria. This lake receives wastewater from different origins. Thus, we assessed the level of pollution through the induction of detoxification activities in tissues of barbel, evaluating simultaneously the suitability of this species to be used as a sentinel. Fish were collected between March 2015 and January 2016 at three locations taking into account the pollution sources and accessibility...
April 7, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28393244/constitutive-androstane-receptor-activation-promotes-bilirubin-clearance-in-a-murine-model-of-alcoholic-liver-disease
#9
Xiuyan Wang, Liyu Zheng, Jinming Wu, Binbin Tang, Mengqin Zhang, Debin Zhu, Xianfan Lin
Increased plasma levels of bilirubin have been reported in rat models and patients with alcoholic liver disease (ALD). The constitutive androstane receptor (CAR) is a known xenobiotic receptor, which induces the detoxification and transport of bilirubin. In the present study, the bilirubin transport regulatory mechanisms, and the role of CAR activation in hepatic and extrahepatic bilirubin clearance were investigated in a murine model of ALD. The mice were fed a Lieber-DeCarli ethanol diet or an isocaloric control diet for 4 weeks, followed by the administration of CAR agonists, 1,4-bis-[2‑(3,5-dichlorpyridyloxy)]benzene (TCPOBOP) and phenobarbital (PB), and their vehicles to examine the effect of the pharmacological activation of CAR on serum levels of bilirubin and on the bilirubin clearance pathway in ALD by serological survey, western blotting and reverse transcription‑quantitative polymerase chain reaction...
April 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28384517/biomarker-response-and-hypothalamus-pituitary-interrenal-axis-functioning-in-arctic-charr-from-bj%C3%A3-rn%C3%A3-ya-74%C3%A2-30-%C3%A2-n-norway-with-high-levels-of-organohalogenated-compounds
#10
Even H Jørgensen, Alec G Maule, Anita Evenset, Guttorm Christensen, Jenny Bytningsvik, Marianne Frantzen, Vladimir Nikiforov, Erin Faught, Mathilakath M Vijayan
The populations of Arctic charr (Salvelinus alpinus) residing in Lake Ellasjøen at Bjørnøya Island in the Norwegian Arctic (74° 30'N, 19° 00'E) possess substantially higher levels of organohalogenated compounds (strongly dominated by polychlorinated biphenyls, PCBs) than conspecifics residing in other, proximate lakes on the island. In the present study we sampled large (<400g), immature charr from Lake Ellasjøen (high PCB levels) and Lake Laksvatn (reference lake, low PCB levels) by hook and line for an immediate blood sampling, and blood and tissue sampling after a 1h confinement stressor...
March 20, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28371246/long-term-liver-specific-functions-of-hepatocytes-in-electrospun-chitosan-nanofiber-scaffolds-coated-with-fibronectin
#11
Divya Rajendran, Ali Hussain, Derek Yip, Amit Parekh, Anil Shrirao, Cheul H Cho
In this study, a new 3-D liver model was developed using biomimetic nanofiber scaffolds and co-culture system consisting of hepatocytes and fibroblasts for the maintenance of long-term liver functions. The chitosan nanofiber scaffolds were fabricated by the electrospinning technique. To enhance cellular adhesion and spreading, the surfaces of the chitosan scaffolds were coated with fibronectin by adsorption and evaluated for various cell types. Cellular phenotype, protein expression, and liver-specific functions were extensively characterized by immunofluorescent and histochemical stainings, albumin ELISA and Cytochrome p450 detoxification assays, and SEM...
March 28, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28366651/the-impact-of-porous-silicon-nanoparticles-on-human-cytochrome-p450-metabolism-in-human-liver-microsomes-in-vitro
#12
Elisa Ollikainen, Dongfei Liu, Arttu Kallio, Ermei Mäkilä, Hongbo Zhang, Jarno Salonen, Hélder A Santos, Tiina M Sikanen
Engineered nanoparticles are increasingly used as drug carriers in pharmaceutical formulations. This study focuses on the hitherto unaddressed impact of porous silicon (PSi) nanoparticles on human cytochrome P450 (CYP) metabolism, which is the major detoxification route of most pharmaceuticals and other xenobiotics. Three different surface chemistries, including thermally carbonized PSi (TCPSi), aminopropylsilane-modified TCPSi (APTES-TCPSi) and alkyne-terminated thermally hydrocarbonized PSi (Alkyne-THCPSi), were compared for their effects on the enzyme kinetics of the major CYP isoforms (CYP1A2, CYP2A6, CYP2D6, and CYP3A4) in human liver microsomes (HLM) in vitro...
March 31, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28362311/quantitative-analysis-of-glutathione-and-cysteine-s-conjugates-of-microcystin-lr-in-the-liver-kidney-and-muscle-of-common-carp-cyprinus-carpio-in-lake-taihu
#13
Laiyan Wu, Songbo Wang, Min Tao, Ping Xie, Jun Chen
Tissue distribution of microcystin (MC)-LR-GSH, MC-LR-Cys and MC-LR of omnivorous fish in Lake Taihu was investigated. MC-LR and MC-LR-Cys were detected in liver, kidney and muscle. The concentration of MC-LR in liver and kidney was 0.052 μg g(-1) DW and 0.067 μg g(-1) DW, respectively. MC-LR-Cys appeared to be an important metabolite with average contents of 1.104 μg g(-1) DW and 0.724 μg g(-1) DW in liver and kidney, and the MC-LR-Cys/MC-LR ratio in liver and kidney reaching as high as 21.4 and 10.8. High MC-LR-Cys/MC-LR ratio and a significant correlation between MC-LR-Cys and MC-LR concentration in liver, suggest that liver is more active in detoxification of MC-LR by formation of MC-LR-Cys for omnivorous fish...
April 2017: Journal of Water and Health
https://www.readbyqxmd.com/read/28357488/study-on-inter-ethnic-human-differences-in-bioactivation-and-detoxification-of-estragole-using-physiologically-based-kinetic-modeling
#14
Jia Ning, Jochem Louisse, Bert Spenkelink, Sebastiaan Wesseling, Ivonne M C M Rietjens
Considering the rapid developments in food safety in the past decade in China, it is of importance to obtain insight into what extent safety and risk assessments of chemicals performed for the Caucasian population apply to the Chinese population. The aim of the present study was to determine physiologically based kinetic (PBK) modeling-based predictions for differences between Chinese and Caucasians in terms of metabolic bioactivation and detoxification of the food-borne genotoxic carcinogen estragole. The PBK models were defined based on kinetic constants for hepatic metabolism derived from in vitro incubations using liver fractions of the two ethnic groups, and used to evaluate the inter-ethnic differences in metabolic activation and detoxification of estragole...
March 29, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28353446/decline-and-changing-profile-of-hepatitis-delta-among-injection-drug-users-in-spain
#15
Antonio Aguilera, Rocio Trastoy, Pablo Barreiro, José Javier Costa, Carmen de Mendoza, Jose M Peña, Vicente Soriano
BACKGROUND: Roughly 15 million people worldwide have hepatitis delta, the most severe form of chronic viral hepatitis that often leads to cirrhosis and liver cancer. Injection drug users (IDUs) are the largest HDV reservoir. Their resurgence in North America and Europe may represent a new opportunity for HDV widespread. METHODS: We examined all consecutive active IDUs seen for the first time and enrolled in detoxification programs at two clinics in Spain during two periods (1993-1996 and 2011-2014, respectively)...
March 29, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28322010/cholesterol-can-modulate-mitochondrial-aquaporin-8-expression-in-human-hepatic-cells
#16
Mauro Danielli, Alejo M Capiglioni, Julieta Marrone, Giuseppe Calamita, Raúl A Marinelli
Hepatocyte mitochondrial aquaporin-8 (mtAQP8) works as a multifunctional membrane channel protein that facilitates the uptake of ammonia for its detoxification to urea as well as the mitochondrial release of hydrogen peroxide. Since early oligonucleotide microarray studies in liver of cholesterol-fed mice showed an AQP8 downregulation, we tested whether alterations of cholesterol content per se modulate mtAQP8 expression in human hepatocyte-derived Huh-7 cells. Cholesterol loading with methyl-β-cyclodextrin (mβCD):cholesterol complexes downregulated the proteolytic activation of cholesterol-responsive sterol regulatory element-binding protein (SREBP) transcriptions factors 1 and 2, and the expression of the target gene 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)...
March 20, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28304107/the-percutaneous-toxicokinetics-of-sulphur-mustard-in-a-damaged-skin-porcine-model-and-the-evaluation-of-woundstat%C3%A2-as-a-topical-decontaminant
#17
Charlotte A Hall, Helen L Lydon, Christopher H Dalton, J Kevin Chipman, John S Graham, Robert P Chilcott
This study used a damaged skin, porcine model to evaluate the in vivo efficacy of WoundStat™ for decontamination of superficial (non-haemorrhaging), sulphur mustard-contaminated wounds. The dorsal skin of 12 female pigs was subjected to controlled physical damage and exposed to 10 μL (14) C-radiolabelled sulphur mustard ((14) C-SM). Animals were randomly assigned to either a control or a treatment group. In the latter, WoundStat™ was applied 30 s post exposure and left in situ for 1 h. Skin lesion progression and decontaminant efficacy were quantified over 6 h using a range of biophysical measurements...
March 17, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28301072/pre-conditions-for-eliminating-mitochondrial-dysfunction-and-maintaining-liver-function-after-hepatic-ischaemia-reperfusion
#18
REVIEW
Chenxia Hu, Lanjuan Li
The liver, the largest organ with multiple synthesis and secretion functions in mammals, consists of hepatocytes and Kupffer, stem, endothelial, stellate and other parenchymal cells. Because of early and extensive contact with the external environment, hepatic ischaemia reperfusion (IR) may result in mitochondrial dysfunction, autophagy and apoptosis of cells and tissues under various pathological conditions. Because the liver requires a high oxygen supply to maintain normal detoxification and synthesis functions, it is extremely susceptible to ischaemia and subsequent reperfusion with blood...
March 16, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28300668/protective-effects-of-coffee-against-oxidative-stress-induced-by-the-tobacco-carcinogen-benzo-%C3%AE-pyrene
#19
Sandra Kalthoff, Steffen Landerer, Julia Reich, Christian P Strassburg
AIMS: Coffee consumption has been epidemiologically associated with a lower risk for liver cirrhosis and cancer. UDP-glucuronosyltransferases (UGT1A) catalyze the detoxification of reactive metabolites thereby acting as indirect antioxidants. Aim of the study was to examine UGT1A regulation in response to Benzo[α]pyrene (BaP) to elucidate the potentially protective effects of coffee on BaP-induced oxidative stress and toxicity. RESULTS: In cell culture (HepG2, KYSE70 cells) and in htgUGT1A-WT mice, UGT1A transcription was activated by BaP, while it was reduced or absent htgUGT1A-SNP (containing 10 commonly occurring UGT1A-SNPs) mice...
March 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28290496/transcriptome-analysis-of-a-wild-bird-reveals-physiological-responses-to-the-urban-environment
#20
Hannah Watson, Elin Videvall, Martin N Andersson, Caroline Isaksson
Identifying the molecular basis of environmentally induced phenotypic variation presents exciting opportunities for furthering our understanding of how ecological processes and the environment can shape the phenotype. Urban and rural environments present free-living organisms with different challenges and opportunities, which have marked consequences for the phenotype, yet little is known about responses at the molecular level. We characterised transcriptomes from an urban and a rural population of great tits Parus major, demonstrating striking differences in gene expression profiles in both blood and liver tissues...
March 14, 2017: Scientific Reports
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