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https://www.readbyqxmd.com/read/28482697/biotransformation-enzyme-activities-and-phase-i-metabolites-analysis-in-litopenaeus-vannamei-following-intramuscular-administration-of-t-2-toxin
#1
Yijia Deng, Yaling Wang, Lijun Sun, Pengli Lu, Rundong Wang, Lin Ye, Defeng Xu, Riying Ye, Ying Liu, Siyuan Bi, Ravi Gooneratne
T-2 toxin (T-2) is a type-A trichothecene produced by Fusarium that causes toxicity to animals. T-2 contamination of grain-based aquatic feed is a concern for the industries related to edible aquatic crustacean species such as the shrimp industry because it can lead to serious food safety issues. T-2, its metabolites, and selected phase I (EROD, CarE) and phase II (GST, UGT, SULT) detoxification enzymes in hemolymph and tissues were monitored at 0, 5, 10 15, 30, 45, and 60 min following T-2 intramuscular administration (3 mg/kg bw) in shrimp (Litopenaeus vannamei)...
May 8, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/28454052/a-multi-biomarker-approach-in-scallop-chlamys-farreri-to-assess-the-impact-of-contaminants-in-qingdao-coastal-area-of-china
#2
Ruiming Guo, Luqing Pan, Rongwang Ji
A multi-biomarker approach was carried out to classify the environmental quality and the adverse effects of contaminants on scallop Chlamys farreri. The scallops were collected from three sampling stations in Qingdao coastal area of China in March, May, August and October of 2015. A suite of environmental factors and biomarkers, including temperature, salinity, pH, the concentrations of polycyclic aromatic hydrocarbons (PAHs), tetrabromobisphenol A (TBBPA) and metals (Cr, Mn, Cu, Zn, Cd, Pb, As) in seawater and soft tissue, mRNA expression of aryl hydrocarbon receptor (AhR) and P-glycoprotein (P-gp), 7-ethoxyresorufin O-deethylase (EROD), glutathione-S-transferase (GST), uridine-diphosphate-glucuronyl-transferase (UGT), sulfotransferase (SULT), metallothionein (MT), Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), lipid peroxidation (LPO) and protein carbonyl (PC) contents and DNA strand breaks, were measured in the gill and digestive gland...
August 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28441724/multiple-udp-glucuronosyltransferase-and-sulfotransferase-enzymes-are-responsible-for-the-metabolism-of-verproside-in-human-liver-preparations
#3
Ju-Hyun Kim, Deok-Kyu Hwang, Ju-Yeon Moon, Yongnam Lee, Ji Seok Yoo, Dae Hee Shin, Hye Suk Lee
Verproside, an active iridoid glycoside component of Veronica species, such as Pseudolysimachion rotundum var. subintegrum and Veronica anagallis-aquatica, possesses anti-asthma, anti-inflammatory, anti-nociceptive, antioxidant, and cytostatic activities. Verproside is metabolized into nine metabolites in human hepatocytes: verproside glucuronides (M1, M2) via glucuronidation, verproside sulfate (M3) via sulfation, picroside II (M4) and isovanilloylcatalpol (M5) via O-methylation, M4 glucuronide (M6) and M4 sulfate (M8) via further glucuronidation and sulfation of M4, and M5 glucuronide (M7) and M5 sulfate (M9) via further glucuronidation and sulfation of M5...
April 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28411281/long-term-stability-of-cryopreserved-human-hepatocytes-evaluation-of-phase-i-and-ii-drug-metabolizing-enzyme-activities-and-cyp3a4-5-induction-for-more-than-a-decade
#4
Miyako Sudo, Mitsuhiro Nishihara, Junzo Takahashi, Satoru Asahi
We evaluated the long term stability of hepatocytes stored in vapor phase of liquid nitrogen for their viability, cytochrome P450 (CYP) 1A2 activity, CYP3A4/5 activity, uridine diphosphate-glucuronosyl transferase (UGT) activity, sulfotransferase (SULT) activity, and CYP3A4/5 induction during 14 years of preservation. No substantial degradation of viability, CYP1A2 activity, UGT activity, or CYP3A4/5 induction was observed. CYP3A4/5 activity showed a slight decrease after 7 years of storage, and SULT activity gradually decreased during storage, although substantial activities remained even after 14 years...
April 14, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28396528/human-enterocytes-as-an-in-vitro-model-for-the-evaluation-of-intestinal-drug-metabolism-characterization-of-drug-metabolizing-enzyme-activities-of-cryopreserved-human-enterocytes-from-twenty-four-donors
#5
Ming-Chih David Ho, Nick Ring, Kirsten Amaral, Utkarsh Doshi, Albert Li
We report here successful isolation and cryopreservation of enterocytes from human small intestine. The enterocytes were isolated by enzyme digestion of the intestinal lumen followed by partial purification via differential centrifugation. The enterocytes were cryopreserved directly after isolation without culturing to maximize retention of in vivo drug metabolizing enzyme activities. Post-thaw viability of the cryopreserved enterocytes was consistently over 80% based on trypan blue exclusion. Cryopreserved enterocytes pooled from 8 donors (4 male and 4 female) were evaluated for their metabolism of 14 pathway-selective substrates: CYP1A2 (phenacetin hydroxylation), CYP2A6 (coumarin 7-hydroxylation), CYP2B6 (bupropion hydroxylation), CYP2C8 (paclitaxel 6α-hydroxylation), CYP2C9 (diclofenac 4-hydroxylation), CYP2C19 (s-mephenytoin 4-hydroxylation), CYP2D6 (dextromethorphan hydroxylation), CYP2E1 (chlorzoxazone 6-hydroxylation), CYP3A4 (midazolam 1'-hydroxylation and testosterone 6β-hydroxylation), CYP2J2 (astemizole O-demethylation), UDP-glucuronosyltransferase (UGT; 7-hydroxycoumarin glucuronidation), sulfotransferase (SULT; 7-hydroxycoumarin sulfation), and carboxylesterase 2 (CES2; irinotecan hydrolysis) activities...
April 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28356314/high-throughput-and-reliable-isotope-label-free-approach-for-profiling-24-metabolic-enzymes-in-fvb-mice-and-gender-differences
#6
Jiamei Chen, Lijun Zhu, Xiaoyan Li, Haihui Zheng, Tongmeng Yan, Cong Xie, Sijing Zeng, Jia Yu, Huangyu Jiang, Linlin Lu, Xiaoxiao Qi, Ying Wang, Ming Hu, Zhongqiu Liu
FVB mice are extensively used in transgenic and pharmacokinetic research. In this study, a validated isotope label-free method of using ultrahigh-performance liquid chromatography (UHPLC)-MS/MS was established for quantifying 24 drug-metabolizing enzymes (DMEs) in FVB mice. The DMEs include cytochrome P450 (CYPs/Cyps), UDP-glucuronsyltransferases (UGTs/Ugts), and sulfotransferases (SULTs/Sults), which are the major phase I and II metabolic enzymes responsible for clearing and detoxifying xenobiotic and endogenous substances...
March 29, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28336091/altered-cellular-metabolism-of-hepg2-cells-caused-by-microcystin-lr
#7
Junguo Ma, Yiyi Feng, Siyu Jiang, Xiaoyu Li
This study aimed to evaluate the possible effects of microcystin-LR (MC-LR) exposure on the metabolism and drug resistance of human hepatocellular carcinoma (HepG2) cells. For this purpose, we first conducted an experiment to make sure that MC-LR could penetrate the HepG2 cell membrane effectively. The transcriptional levels of phase I (such as CYP2E1, CYP3A4, and CYP26B1) and phase II (such as EPHX1, SULTs, and GSTM) enzymes and export pump genes (such as MRP1 and MDR1) were altered by MC-LR-exposure for 24 h, indicating that MC-LR treatment may destabilize the metabolism of HepG2 cells...
March 21, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28326452/methyleugenol-dna-adducts-in-human-liver-are-associated-with-sult1a1-copy-number-variations-and-expression-levels
#8
Roman Tremmel, Kristin Herrmann, Wolfram Engst, Walter Meinl, Kathrin Klein, Hansruedi Glatt, Ulrich M Zanger
Methyleugenol is a rodent hepatocarcinogen occurring in many herbs and spices as well as essential oils used for flavoring. Following metabolic activation by cytochromes P450 (CYPs) and sulfotransferases (SULTs), methyleugenol can form DNA adducts. Previously, we showed that DNA adduct formation by methyleugenol in mouse liver is dependent on SULT1A1 expression and that methyleugenol DNA adducts are abundant in human liver specimens. In humans, SULT1A1 activity is affected by genetic polymorphisms, including single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs)...
March 22, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28303724/non-alcoholic-fatty-liver-disease-nafld-pathogenesis-classification-and-effect-on-drug-metabolizing-enzymes-and-transporters
#9
Enoch Cobbina, Fatemeh Akhlaghi
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. It is defined by the presence of steatosis in more than 5% of hepatocytes with little or no alcohol consumption. Insulin resistance, the metabolic syndrome or type 2 diabetes and genetic variants of PNPLA3 or TM6SF2 seem to play a role in the pathogenesis of NAFLD. The pathological progression of NAFLD follows tentatively a "three-hit" process namely steatosis, lipotoxicity and inflammation. The presence of steatosis, oxidative stress and inflammatory mediators like TNF-α and IL-6 has been implicated in the alterations of nuclear factors such as CAR, PXR, PPAR-α in NAFLD...
March 17, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28286122/regioselective-production-of-sulfated-polyphenols-using-human-cytosolic-sulfotransferase-expressing-escherichia-coli-cells
#10
Takehiko Shimohira, Katsuhisa Kurogi, Takuyu Hashiguchi, Ming-Cheh Liu, Masahito Suiko, Yoichi Sakakibara
Dietary polyphenols present in fruits and vegetables have been reported to manifest beneficial health effects on humans. Polyphenol metabolites including their sulfated derivatives have been shown to be biologically active. Primarily due to the difficulty in preparing regiospecific sulfated polyphenols for detailed investigations, the exact functions of sulfated polyphenols, however, remain unclear. The current study aimed to develop a procedure for the regioselective production of sulfated polyphenols using Escherichia coli cells expressing human cytosolic sulfotransferases (SULTs)...
March 9, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28278373/potential-metabolic-activation-of-a-representative-c4-alkylated-polycyclic-aromatic-hydrocarbon-retene-1-methyl-7-isopropyl-phenanthrene-associated-with-the-deepwater-horizon-oil-spill-in-human-hepatoma-hepg2-cells
#11
Meng Huang, Clementina Mesaros, Linda C Hackfeld, Richard P Hodge, Tianzhu Zang, Ian A Blair, Trevor M Penning
Exposure to petrogenic polycyclic aromatic hydrocarbons (PPAHs) in the food chain is the major human health hazard associated with the Deepwater Horizon oil spill. C4-Phenanthrenes are representative PPAHs present in the crude oil and could contaminate the seafood. We describe the metabolism of a C4-phenanthrene regioisomer retene (1-methyl-7-isopropyl-phenanthrene) in human HepG2 cells as a model for metabolism in human hepatocytes. Retene because of its sites of alkylation cannot be metabolized to a diol-epoxide...
April 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28250318/characterization-of-species-differences-in-xenobiotic-metabolism-in-non-experimental-animals
#12
REVIEW
Hazuki Mizukawa, Yoshinori Ikenaka, Mayu Kakehi, Shouta Nakayama, Mayumi Ishizuka
 The ability to metabolize xenobiotics in organisms has a wide degree of variation among organisms. This is caused by differences in the pattern of xenobiotic bioaccumulation among organisms, which affects their tolerance. It has been reported in the veterinary field that glucuronidation (UGT) activity in cats, acetylation activity in dogs and sulfation (SULT) activity in pigs are sub-vital in these species, respectively, and require close attention when prescribing the medicine. On the other hand, information about species differences in xenobiotics metabolism remains insufficient, especially in non-experimental animals...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28225918/the-aplication-of-cyanoacrilate-surgical-glue-on-skin-suture-in-rats
#13
João Ilgenfritz, Ricardo Dutra Aydos, Iandara Schettert Silva, Rondon Tosta Ramalho, João Ilgenfritz, Gerson Gattats Orro de Campos, Ricardo Kenithi Nakamura, Danilo M Zanello Guerisoli, Wilson de Barros Cantero
Purpose: To compare the use of a new cyanoacrylate-based surgical glue and suture with sepa-rate points in skin wounds closure. Methods: Thirty-six rats were subjected to a 4cm dorsal longitudinal incision. Twelve were sub-jected to simple suture with polyamide 6-0, 12 rats underwent wall synthesis using Dermabond(r) and 12 was performed cutaneous synthesis with N-2-Butyl-Cyanoacrylate. Twelve of each group was euthanized on the seventh postoperative day, their blood was taken to biochemical tests and a layer of skin and subcutaneous tissue surrounding the surgical scar was randomly divided in two segments, to the submission of tension tests and to histological study...
January 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/28222028/expression-purification-and-characterization-of-human-cytosolic-sulfotransferase-sult-1c4
#14
Amber L Guidry, Zachary E Tibbs, Melissa Runge-Morris, Charles N Falany
Human cytosolic sulfotransferase 1C4 (hSULT1C4) is a dimeric Phase II drug-metabolizing enzyme primarily expressed in the developing fetus. SULTs facilitate the transfer of a hydrophilic sulfonate moiety from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) onto an acceptor substrate altering the substrate's biological activity and increasing the compound's water solubility. While several of the hSULTs' endogenous and xenobiotic substrates have been identified, the physiological function of hSULT1C4 remains unknown...
January 1, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28177672/a-reappraisal-of-the-6-o-desmethylnaproxen-sulfating-activity-of-the-human-cytosolic-sulfotransferases
#15
Fatemah A Alherz, Daniyah A Almarghalani, Noor A Hussein, Katsuhisa Kurogi, Ming-Cheh Liu
In this study, we aimed to obtain a comprehensive account of the human cytosolic sulfotransferases (SULTs) that are capable of sulfating 6-O-desmethylnaproxen (O-DMN), a major metabolite of naproxen. Of the 13 known human SULTs tested, 7 (SULT1A1, SULT1A2, SULT1A3, SULT1B1, SULT1C2, SULT1C4, and SULT1E1) displayed O-DMN-sulfating activity, when analyzed using an elevated substrate concentration (500 μmol·L(-1)) together with 14 μmol·L(-1) of the sulfate donor, 3'-phosphoadenosine-5'-phosphosulfate (PAPS)...
January 22, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28160514/deep-learning-for-polyp-recognition-in-wireless-capsule-endoscopy-images
#16
Yixuan Yuan, Max Q-H Meng
PURPOSE: Wireless capsule endoscopy (WCE) enables physicians to examine the digestive tract without any surgical operations, at the cost of a large volume of images to be analyzed. In the computer-aided diagnosis of WCE images, the main challenge arises from the difficulty of robust characterization of images. This study aims to provide discriminative description of WCE images and assist physicians to recognize polyp images automatically. METHODS: We propose a novel deep feature learning method, named stacked sparse autoencoder with image manifold constraint (SSAEIM), to recognize polyps in the WCE images...
April 2017: Medical Physics
https://www.readbyqxmd.com/read/28160022/role-of-human-sulfotransferase-1a1-and-n-acetyltransferase-2-in-the-metabolic-activation-of-16-heterocyclic-amines-and-related-heterocyclics-to-genotoxicants-in-recombinant-v79-cells
#17
Matthieu Chevereau, Hansruedi Glatt, Daniel Zalko, Jean-Pierre Cravedi, Marc Audebert
Heterocyclic aromatic amines (HAAs) are primarily produced during the heating of meat or fish. HAAs are mutagenic and carcinogenic, and their toxicity in model systems depend on metabolic activation. This activation is mediated by cytochrome P450 (CYP) enzymes, in particular CYP1A2. Some studies have indicated a role of human sulfotransferase (SULT) 1A1 and N-acetyltransferase (NAT) 2 in the terminal activation of HAAs. In this study, we conducted a metabolism/genotoxicity relationship analysis for 16 HAAs and related heterocyclics...
February 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28070880/on-the-molecular-basis-underlying-the-metabolism-of-tapentadol-through-sulfation
#18
Ahsan F Bairam, Mohammed I Rasool, Katsuhisa Kurogi, Ming-Cheh Liu
BACKGROUND AND OBJECTIVES: Previous studies reported that tapentadol-sulfate represented one of the major metabolites of tapentadol excreted in urine. The current study aimed to identify the human cytosolic sulfotransferases (SULTs) that is(are) capable of sulfating tapentadol and to examine whether human cells and human organ specimens are capable of sulfating tapentadol. METHODS: Thirteen human SULTs, previously expressed and purified, as well as human organ cytosols, were analyzed for tapentadol-sulfating activity using an established sulfotransferase assay...
January 10, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28062095/the-liver-transcriptome-of-suckermouth-armoured-catfish-pterygoplichthys-anisitsi-loricariidae-identification-of-expansions-in-defensome-gene-families
#19
Thiago E Parente, Daniel A Moreira, Maithê G P Magalhães, Paula C C de Andrade, Carolina Furtado, Brian J Haas, John J Stegeman, Mark E Hahn
Pterygoplichthys is a genus of related suckermouth armoured catfishes native to South America, which have invaded tropical and subtropical regions worldwide. Physiological features, including an augmented resistance to organic xenobiotics, may have aided their settlement in foreign habitats. The liver transcriptome of Pterygoplichthys anisitsi was sequenced and used to characterize the diversity of mRNAs potentially involved in the responses to natural and anthropogenic chemicals. In total, 66,642 transcripts were assembled...
February 15, 2017: Marine Pollution Bulletin
https://www.readbyqxmd.com/read/28055299/guiding-bispecific-monovalent-antibody-formation-through-proteolysis-of-igg1-single-chain
#20
Nazzareno Dimasi, Ryan Fleming, Kris F Sachsenmeier, Binyam Bezabeh, Carl Hay, Jincheng Wu, Erin Sult, Saravanan Rajan, Li Zhuang, Peter Cariuk, Andrew Buchanan, Michael A Bowen, Herren Wu, Changshou Gao
We developed an IgG1 domain-tethering approach to guide the correct assembly of 2 light and 2 heavy chains, derived from 2 different antibodies, to form bispecific monovalent antibodies in IgG1 format. We show here that assembling 2 different light and heavy chains by sequentially connecting them with protease-cleavable polypeptide linkers results in the generation of monovalent bispecific antibodies that have IgG1 sequence, structure and functional properties. This approach was used to generate a bispecific monovalent antibody targeting the epidermal growth factor receptor and the type I insulin-like growth factor receptor that: 1) can be produced and purified using standard IgG1 techniques; 2) exhibits stability and structural features comparable to IgG1; 3) binds both targets simultaneously; and 4) has potent anti-tumor activity...
April 2017: MAbs
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