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https://www.readbyqxmd.com/read/29318967/inter-individual-variability-in-activity-of-the-major-drug-metabolizing-enzymes-in-liver-homogenates-of-20-individuals
#1
J Chris Vos, Shalenie P den Braver-Sewradj, Michiel W den Braver, Marc van Dijk, Yongjie Zhang, Stefan J Dekker, Lukas Wijaya, Nico P E Vermeulen, Lysiane Richert, Jan N M Commandeur
BACKGROUND: Inter-individual variability in hepatic drug metabolizing enzyme (DME) activity is a major contributor to heterogeneity in drug clearance and safety. Accurate data on expression levels and activities of DMEs is an important prerequisite for in vitro-in vivo extrapolation and in silico based predictions. Characterization and assessment of inter-correlations of the major DMEs cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs) have been extensively documented, but simultaneous quantification including other major DMEs has been lacking...
January 8, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29316750/-study-the-impacts-of-diagnosis-on-occupational-noise-induced-deafness-after-bring-into-the-different-high-frequency-hearing-threshold-weighted-value
#2
L J Xue, A C Yang, H Chen, W X Huang, J J Guo, X Y Liang, Z Q Chen, Q L Zheng
Objective: Study of the results and the degree on occupational noise-induced deafness in-to the different high frequency hearing threshold weighted value, in order to provide theoretical basis for the re-vision of diagnostic criteria on occupational noise-induced deafness. Methods: A retrospective study was con-ducted to investigate the cases on the diagnosis of occupational noise-induced deafness in Guangdong province hospital for occupational disease prevention and treatment from January 2016 to January 2017...
November 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/29316515/the-body-burden-and-thyroid-disruption-in-lizards-eremias-argus-living-in-benzoylurea-pesticides-contaminated-soil
#3
Jing Chang, Jitong Li, Weiyu Hao, Huili Wang, Wei Li, Baoyuan Guo, Jianzhong Li, Yinghuan Wang, Peng Xu
Dermal exposure is regarded as a potentially significant but understudied route for pesticides uptake in terrestrial reptiles. In this study, a native Chinese lizard was exposed to control, diflubenzuron or flufenoxuron contaminated soil (1.5 mg kg-1) for 35 days. Tissue distribution, liver lesions, thyroid hormone levels and transcription of most target genes were examined. The half-lives of diflubenzuron and flufenoxuron in the soil were 118.9 and 231.8 days, respectively. The accumulation of flufenoxuron in the liver, brain, kidney, heart, plasma and skin (1...
January 4, 2018: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29237391/utility-of-pooled-cryopreserved-human-enterocytes-as-an-in-vitro-model-for-assessing-intestinal-clearance-and-drug-drug-interactions
#4
Zhengyin Yan, Susan Wong, Jane Kelly, Hoa Le, Ning Liu, Mika Kosaka, Suzanne Tey, Peter Vuong, Albert Li
A recent advancement in isolation and cryopreservation has resulted in commercially available primary human enterocytes that express various drug metabolizing enzymes (DMEs) and transporters. The main objective of this study was to further evaluate the utility of pooled cryopreserved enterocytes, specifically MetMax™ cryopreserved human enterocytes (In Vitro ADMET Laboratories), as an in vitro model for assessing intestinal clearance in comparison to hepatocytes. It was found that, for CYP3A4 substrates such as midazolam, amprenavir and loperamide, in vitro metabolic clearance is generally lower in enterocytes compared to that of hepatocytes, which is consistent with the relative abundance of the enzyme between the intestine and liver...
December 12, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/29231856/involvement-of-udp-glucuronosyltransferases-and-sulfotransferases-in-the-excretion-and-tissue-distribution-of-resveratrol-in-mice
#5
Michaela Böhmdorfer, Akos Szakmary, Robert H Schiestl, Javier Vaquero, Juliane Riha, Stefan Brenner, Theresia Thalhammer, Thomas Szekeres, Walter Jäger
Resveratrol is a naturally occurring polyphenolic compound with various pharmacological activities. It is unknown whether the expression of metabolizing enzymes correlates with resveratrol levels in organs and tissues. Therefore, we investigated the metabolism and tissue distribution of resveratrol in mice and assessed its association with the expression of UDP-glucuronosyltransferase (Ugt) and sulfotransferase (Sult) genes. Plasma, urine, feces, and various organs were analyzed using high-performance liquid chromatography at up to 8 h after intragastric resveratrol administration...
December 12, 2017: Nutrients
https://www.readbyqxmd.com/read/29226673/multiplexed-detection-of-attomole-nucleic-acids-using-fluorescent-nanoparticle-counting-platform
#6
Xiaojing Pei, Haoyan Yin, Tiancheng Lai, Jun-Long Zhang, Feng Liu, Xiao Xu, Na Li
The sensitive multiplexed detection of nucleic acids in a single sample by a simple manner is of pivotal importance for diagnosis and therapy of human diseases. Herein, we constructed an automatic fluorescent nanoparticle (FNP) counting platform with a common fluorescence microscopic imaging setup for non-amplification multiplexed detection of attomole nucleic acids. Taking the ad-vantages of the highly bright, multi-color emitting FNPs and magnetic separation, the platform enables the sensitive multiplexed detection without the need for extra fluorescent labels...
December 11, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29148714/evaluating-the-rate-and-substrate-specificity-of-laboratory-evolved-xna-polymerases
#7
Ali Nikoomanzar, Matthew R Dunn, John C Chaput
Engineered polymerases that can copy genetic information between DNA and xeno-nucleic acids (XNA) hold tremendous value as reagents in future biotechnology applications. However, current XNA polymerases function with inferior activity relative to their natural counterparts, indicating that current polymerase engineering efforts would benefit from new benchmarking assays. Here, we describe a highly parallel, low-cost method for measuring the average rate and substrate specificity of XNA polymerases in a standard qPCR instrument...
November 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29134333/whole-cell-dependent-biosynthesis-of-sulfo-conjugate-using-human-sulfotransferase-expressing-budding-yeast
#8
Miyu Nishikawa, Yuuka Masuyama, Motomichi Nunome, Kaori Yasuda, Toshiyuki Sakaki, Shinichi Ikushiro
Cytosolic sulfotransferases (SULTs), one of the predominant phase II drug metabolizing enzymes (DME), play important roles in metabolism of xeno- and endobiotics to generate their sulfo-conjugates. These sulfo-conjugates often have biological activities but are difficult to study, because even though only small amounts are required to evaluate their efficacy and safety, chemical or biological synthesis of sulfo-conjugatesis is often challenging. Previously, we constructed a DME expression system for cytochrome P450 and UGT, using yeast cells, and successfully produced xenobiotic metabolites in a whole-cell-dependent manner...
November 13, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29130021/transgenic-overexpression-of-steroid-sulfatase-alleviates-cholestasis
#9
Mengxi Jiang, Meishu Xu, Songrong Ren, Kyle W Selcer, Wen Xie
Background and Aim: Sulfotransferase (SULT)-mediated sulfation and steroid sulfatase (STS)-mediated desulfation represent two critical mechanisms that regulate the chemical and functional homeostasis of endogenous and exogenous molecules. STS catalyzes the hydrolysis of steroid sulfates to form hydroxysteroids. Oxygenated cholesterol derivative oxysterols are known to be endogenous ligands of the liver X receptor (LXR), a nuclear receptor with anti-cholestasis activity, whereas the sulfated oxysterols antagonize LXR signaling...
June 2017: Liver Research
https://www.readbyqxmd.com/read/29126297/tellurate-enters-escherichia-coli-k-12-cells-via-the-sult-type-sulfate-transporter-cyspuwa
#10
Jennifer Goff, Nathan Yee
Soluble forms of tellurium are environmental contaminants that are toxic to microorganisms. While tellurite [Te(IV)] is a well-characterized antimicrobial agent, little is known about the interactions of tellurate [Te(VI)] with bacterial cells. In this study, we investigated the role of sulfate transporters in the uptake of tellurate in Escherichia coli K-12. Mutant strains carrying a deletion of the cysW gene in the CysPUWA sulfate transporter system accumulated less cellular tellurium and exhibited higher resistance to tellurate compared to the wild type strain...
November 6, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29109113/generation-and-characterization-of-sult4a1-mutant-mouse-models
#11
Patrick L Garcia, Mohammed I Hossain, Shaida A Andrabi, Charles N Falany
Sulfotransferase 4A1 (SULT4A1) belongs to the cytosolic sulfotransferase (SULT) superfamily of enzymes that catalyze sulfonation reactions with a variety of endogenous and exogenous substrates. Of the SULTs, SULT4A1 was shown to have the highest sequence homology between vertebrate species, yet no known function or enzymatic activity have been identified for this orphan SULT. To better understand SULT4A1 function in mammalian brain, two mutant SULT4A1 mouse strains were generated utilizing CRISPR-Cas9 technology...
November 6, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29090664/pharmacogenetics-of-metabolic-genes-of-anthracyclines-in-acute-myeloid-leukemia
#12
Juan Eduardo Megias-Vericat, David Martinez-Cuadron, Maria Jose Herrero, Salvador F Alino, Jose Luis Poveda, Miguel Angel Sanz, Pau Montesinos
BACKGROUND: Anthracyclines in combination with cytarabine have been the standard therapy for acute myeloid leukemia (AML) for decades with high efficacy. However, the majority of patients will show initial resistance or will relapse after initial complete remission. Genetic variability in genes involved in anthracyclines metabolic pathway could be one of the causes of the interindividual differences in clinical outcomes. METHODS: A systematic review of published studies in AML cohorts was carried out in order to analyze the influence of polymorphisms in genes of anthracycline metabolism on efficacy and toxicity...
November 1, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29074051/the-inhibitory-effects-of-%C3%AE-caryophyllene-%C3%AE-caryophyllene-oxide-and-%C3%AE-humulene-on-the-activities-of-the-main-drug-metabolizing-enzymes-in-rat-and-human-liver-in-vitro
#13
Linh Thuy Nguyen, Zuzana Myslivečková, Barbora Szotáková, Alena Špičáková, Kateřina Lněničková, Martin Ambrož, Vladimír Kubíček, Kristýna Krasulová, Pavel Anzenbacher, Lenka Skálová
Sesquiterpenes, the main components of plant essential oils, are often taken in the form of folk medicines and dietary supplements. Several sesquiterpenes possess interesting biological activities but they could interact with concurrently administered drugs via inhibition of drug-metabolizing enzymes. Therefore, the present study was designed to test the potential inhibitory effect of tree structurally relative sesquiterpenes β-caryophyllene (CAR), β-caryophyllene oxide (CAO) and α-humulene (HUM) on the activities of the main drug-metabolizing enzymes...
October 23, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29038294/the-nsaid-allosteric-site-of-human-cytosolic-sulfotransferases
#14
Ting Wang, Ian Cook, Thomas S Leyh
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed drugs worldwide - more than 111 million prescriptions were written in the United Sates in 2014. NSAIDs allosterically inhibit cytosolic sulfotransferases (SULTs) with high specificity and therapeutically relevant affinities. The current study focuses on the interactions of SULT1A1 and mefenamic acid (MEF) - a potent, highly specific NSAID inhibitor of 1A1. Here, the first structure of an NSAID allosteric site - the MEF-binding site of SULT1A1 - is determined using spin-label-triangulation NMR...
October 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29022574/osthole-prevents-acetaminophen-induced-liver-injury-in-mice
#15
Yun Cai, Wu Sun, Xin-Xin Zhang, Yan-Die Lin, Hao Chen, Hao Li
Acetaminophen (APAP) overdose leads to severe hepatotoxicity. Osthole, a natural coumarin found in traditional Chinese medicinal herbs, has therapeutic potential in the treatment of various diseases. In this study, we investigated the effects of osthole against APAP-induced hepatotoxicity in mice. Mice were administered osthole (100 mg·kg(-1)·d(-1), ip) for 3 d, then on the fourth day APAP (300 mg/kg, ip) was co-administered with osthole. The mice were euthanized post-APAP, their serum and livers were collected for analysis...
October 12, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28992322/human-cytosolic-sulphotransferase-sult1c3-genomic-analysis-and-functional-characterization-of-splice-variant-sult1c3a-and-sult1c3d
#16
Katsuhisa Kurogi, Takehiko Shimohira, Haruna Kouriki-Nagatomo, Guisheng Zhang, Ethan R Miller, Yoichi Sakakibara, Masahito Suiko, Ming-Cheh Liu
The cytosolic sulphotransferase SULT1C3 remained the most poorly understood human SULT. The SULT1C3 gene has been shown to contain alternative exons 7 and 8, raising the question concerning their evolutionary origin and implying the generation of multiple SULT1C3 variants. Two SULT1C3 splice variants, SULT1C3a and SULT1C3d, were investigated to verify the impact of alternative C-terminal sequences on their sulphating activity. Sequence homology and gene location analyses were performed to verify the orthology of the SULT1C3 gene...
June 29, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28970781/non-digestible-stachyose-promotes-bioavailability-of-genistein-through-inhibiting-intestinal-degradation-and-first-pass-metabolism-of-genistein-in-mice
#17
Yalong Lu, Dehui Lin, Wenfeng Li, Xingbin Yang
This study was designed to explore the molecular mechanism of stachyose in enhancing the gastrointestinal stability and absorption of soybean genistein in mice. Male Kunming mice in each group (n = 8) were administered by intragastric gavage with saline, stachyose (250 mg/kg·bw), genistein (100 mg/kg·bw), and stachyose (50, 250, and 500 mg/kg·bw) together with genistein (100 mg/kg·bw) for 4 consecutive weeks, respectively, and then their urine, feces, blood, gut, and liver were collected. UPLC-qTOF/MS analysis showed that levels of genistein and its metabolites (dihydrogenistein, genistein 7-sulfate sodium salt, genistein 4'-β-D-glucuronide, and genistein 7-β-D-glucuronide) in serum and urine were increased with an increase in stachyose dosages in mice...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28970022/stereoselective-degradation-and-thyroid-endocrine-disruption-of-lambda-cyhalothrin-in-lizards-eremias-argus-following-oral-exposure
#18
Jing Chang, Weiyu Hao, Yuanyuan Xu, Peng Xu, Wei Li, Jianzhong Li, Huili Wang
The disturbance of the thyroid system and elimination of chiral pyrethroid pesticides with respect to enantioselectivity in reptiles have so far received limited attention by research. In this study, bioaccumulation, thyroid gland lesions, thyroid hormone levels, and hypothalamus-pituitary-thyroid axis-related gene expression in male Eremias argus were investigated after three weeks oral administration of lambda-cyhalothrin (LCT) enantiomers. In the lizard liver, the concentration of LCT was negatively correlated with the metabolite-3-phenoxybenzoic acid (PBA) level during 21 days of exposure...
September 29, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28933499/multi-biomarker-approach-in-the-scallop-chlamys-farreri-to-assess-pahs-pollution-in-qingdao-coastal-areas-of-china
#19
Luqing Pan, Mengyu Zhang, Qian Jin, Rongwang Ji
A multi-biomarker approach was conducted in the scallop Chlamys farreri from three sites, denoted here as S1, S2, and S3, in Qingdao coastal areas of China in March, June, September and December 2014 to assess pollution from polycyclic aromatic hydrocarbons (PAHs) and to select appropriate biomarkers. A suite of biological responses of the gills and digestive glands of the scallops was assayed, including: (i) phase I detoxification enzymes of 7-ethoxyresorufin-O-deethylase (EROD), epoxide hydrolase (EH), and dihydrodiol dehydrogenase (DD) and phase II detoxification enzymes of glutathione-S-transferase (GST) and sulfotransferase (SULT); (ii) antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx); (iii) oxidative damage parameters: lipid peroxidation (LPO) expressed by malondialdehyde (MDA) contents, protein carbonylation (PC) and DNA damage (F value); and (iv) the metabolism-related genes of EH, DD, GST, SULT and SOD...
November 15, 2017: Environmental Science. Processes & Impacts
https://www.readbyqxmd.com/read/28911247/metabolic-pathways-and-pharmacokinetics-of-natural-medicines-with-low-permeability
#20
Mei Zeng, Lan Yang, Dan He, Yao Li, Mingxin Shi, Jingqing Zhang
Drug metabolism plays an important role in the drug disposal process. Differences in pharmacokinetics among individuals are the basis for personalized medicine. Natural medicines, formed by long-term evolution of nature, prioritize the action of a target protein with a drug. Natural medicines are valued for structural diversity, low toxicity, low cost, and definite biological activities. Metabolic pathway and pharmacokinetic research of natural medicines is highly beneficial for clinical dose adjustment and the development of personalized medicine...
September 14, 2017: Drug Metabolism Reviews
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