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https://www.readbyqxmd.com/read/28822992/low-dose-bisphenol-a-increases-bile-duct-proliferation-in-juvenile-rats-a-possible-evidence-for-risk-of-liver-cancer-in-the-exposed-population
#1
Ji Seong Jeong, Ki Taek Nam, Buhyun Lee, Aryo Dimas Pamungkas, Daeun Song, Minjeong Kim, Wook-Joon Yu, Jinsoo Lee, Sunha Jee, Youngja H Park, Kyung-Min Lim
Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females...
August 21, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28821316/obesity-and-fatty-liver-are-prevented-by-inhibition-of-the-aryl-hydrocarbon-receptor-in-both-female-and-male-mice
#2
Benjamin J Moyer, Itzel Y Rojas, Joanna S Kerley-Hamilton, Krishnamurthy V Nemani, Heidi W Trask, Carol S Ringelberg, Barjor Gimi, Eugene Demidenko, Craig R Tomlinson
Inhibition of the aryl hydrocarbon receptor (AHR) prevents Western diet-induced obesity and fatty liver in C57Bl/6J (B6) male mice. The AHR is a ligand-activated nuclear receptor that regulates genes involved in xenobiotic metabolism and T-cell differentiation. Here, we tested the hypothesis that AHR antagonism would also prevent obesity and fatty liver in female mice and that B6 mice (higher-affinity AHR) and congenic B6.D2 mice (lower-affinity AHR) would differentially respond to AHR inhibition. Female and male adult B6 and B6...
August 2017: Nutrition Research
https://www.readbyqxmd.com/read/28819546/oxidative-stress-harms-and-benefits-for-human-health
#3
REVIEW
Gabriele Pizzino, Natasha Irrera, Mariapaola Cucinotta, Giovanni Pallio, Federica Mannino, Vincenzo Arcoraci, Francesco Squadrito, Domenica Altavilla, Alessandra Bitto
Oxidative stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products. ROS can play, and in fact they do it, several physiological roles (i.e., cell signaling), and they are normally generated as by-products of oxygen metabolism; despite this, environmental stressors (i.e., UV, ionizing radiations, pollutants, and heavy metals) and xenobiotics (i.e., antiblastic drugs) contribute to greatly increase ROS production, therefore causing the imbalance that leads to cell and tissue damage (oxidative stress)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28819397/iron-chelators-and-exogenic-photosensitizers-synergy-through-oxidative-stress-gene-expression
#4
Anna Mrozek-Wilczkiewicz, Katarzyna Malarz, Marzena Rams-Baron, Maciej Serda, Daniela Bauer, Franz-Peter Montforts, Alicja Ratuszna, Thomas Burley, Jaroslaw Polanski, Robert Musiol
In non-invasive anticancer photodynamic therapy (PDT), a nontoxic photosensitizer (PS), which is activated by visible light, is used as a magic bullet that selectively destroys cancer cells. Recently, we described the combined therapy of 5-aminolevulinic acid (ALA-PDT) with thiosemicarbazone (TSC), i.e. an iron-chelating agent. This resulted in a strong synergistic effect. Herein, we investigated a novel strategy using a combination of PDT consist of the xenobiotic-porphyrin type PS with TSC. We observed a synergistic effect for all of the pairs of TSC-PS...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819395/downregulation-of-abc-transporters-in-non-neoplastic-tissues-confers-better-prognosis-for-pancreatic-and-colorectal-cancer-patients
#5
Pavel Dvorak, Viktor Hlavac, Beatrice Mohelnikova-Duchonova, Vaclav Liska, Martin Pesta, Pavel Soucek
Transport of a wide variety of substrates, including xenobiotics, is one of the main functions attributed to human ATP-binding cassette (ABC) proteins. Overexpression of ABC genes is considered to be an important mechanism facilitating the development of chemoresistance. Relationships between the expression levels of ABC genes in tumor tissues and established clinicopathological features were extensively studied previously. The current study tested our hypothesis that the expression levels of ABC genes in non-neoplastic (control) tissues also provide important information in relation to the relevant tumor progression...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819225/cytochrome-p450-abc-transporter-inhibition-simultaneously-enhances-ivermectin-pharmacokinetics-in-the-mammal-host-and-pharmacodynamics-in-anopheles-gambiae
#6
Carlos J Chaccour, Felix Hammann, Marta Alustiza, Sandra Castejon, Brian B Tarimo, Gloria Abizanda, Ángel Irigoyen Barrio, Helena Martí Soler, Rafael Moncada, José Ignacio Bilbao, Azucena Aldaz, Marta Maia, José Luis Del Pozo
Mass administration of endectocides, drugs that kill blood-feeding arthropods, has been proposed as a complementary strategy to reduce malaria transmission. Ivermectin is one of the leading candidates given its excellent safety profile. Here we provide proof that the effect of ivermectin can be boosted at two different levels by drugs inhibiting the cytochrome or ABC transporter in the mammal host and the target mosquitoes. Using a mini-pig model, we show that drug-mediated cytochrome P450/ABC transporter inhibition results in a 3-fold increase in the time ivermectin remains above mosquito-killing concentrations...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819071/genetic-and-non-genetic-factors-associated-with-protein-abundance-of-flavin-containing-monooxygenase-3-in-human-liver
#7
Meijuan Xu, Deepak Kumar Bhatt, Catherine K Yeung, Katrina G Claw, Amarjit S Chaudhry, Andrea Gaedigk, Robin E Pearce, Ulrich Broeckel, Roger Gaedigk, Debbie Nickerson, Erin Schuetz, Allan E Rettie, Steven Leeder, Kenneth E Thummel, Bhagwat Prasad
Hepatic flavin-containing monooxygenase 3 (FMO3) metabolizes a broad array of nucleophilic heteroatom (e.g., N or S)-containing xenobiotics (e.g., amphetamine, sulindac, benzydamine, ranitidine, tamoxifen, nicotine, and ethioniamide), as well as endogenous compounds (e.g., catecholamine and trimethylamine). To predict the effect of genetic and non-genetic factors on the hepatic metabolism of FMO3 substrates, we quantified FMO3 protein abundance in human liver microsomes (HLM; n=445) by LC-MS/MS proteomics. Genotyping/gene-resequencing, mRNA expression, and functional activity (with benzydamine as a probe substrate) of FMO3 were also performed...
August 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28818793/cellular-adaptation-to-xenobiotics-interplay-between-xenosensors-reactive-oxygen-species-and-foxo-transcription-factors
#8
Lars-Oliver Klotz, Holger Steinbrenner
Cells adapt to an exposure to xenobiotics by upregulating the biosynthesis of proteins involved in xenobiotic metabolism. This is achieved largely via activation of cellular xenosensors that modulate gene expression. Biotransformation of xenobiotics frequently comes with the generation of reactive oxygen species (ROS). ROS, in turn, are known modulators of signal transduction processes. FOXO (forkhead box, class O) transcription factors are among the proteins deeply involved in the cellular response to stress, including oxidative stress elicited by the formation of ROS...
August 3, 2017: Redox Biology
https://www.readbyqxmd.com/read/28818751/nutritional-modulation-of-intestinal-drug-metabolizing-cytochrome-p450-by-butyrate-of-different-origin-in-chicken
#9
Anna Kulcsár, Gábor Mátis, Andor Molnár, Janka Petrilla, László Wágner, Hedvig Fébel, Ferenc Husvéth, Károly Dublecz, Zsuzsanna Neogrády
Intestinal cytochrome P450 (CYP) enzymes play key role in the first pass metabolism of orally ingested xenobiotics, providing a primary metabolic barrier, being of special importance in maintaining animal health and production. This study was aimed to investigate how intestinal drug-metabolizing CYPs can be modulated by nutritional factors in broiler chicken. We investigated the effects of the natural growth promoter (n-)butyrate of different origin (feed supplementation of protected or non-protected forms and/or inducing caecal microbial production by supporting higher level of dietary non-starch polysaccharides [NSP]) on the activity of duodenal CYPs...
August 1, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28818592/the-impact-of-chemosensitisation-on-bioaccumulation-and-sediment-toxicity
#10
Denise Kurth, Stefan Lips, Riccardo Massei, Martin Krauss, Till Luckenbach, Tobias Schulze, Werner Brack
Cellular multixenobiotic resistance (MXR) transport proteins enhance the efflux of numerous organic pollutants. However, MXR proteins may be blocked or saturated by xenobiotic compounds, acting as inhibitors - also called chemosensitisers. Although effective on a cellular level, the environmental relevance of chemosensitisers has not been conclusively demonstrated. Since sediments are an important source of bioaccumulating compounds in aquatic ecosystems, sediments and sediment-associated hydrophobic pollutants were investigated for their potential to increase exposure and toxicity in the presence of chemosensitisation...
August 9, 2017: Chemosphere
https://www.readbyqxmd.com/read/28813640/innate-immune-signaling-in-the-ventral-tegmental-area-contributes-to-drug-primed-reinstatement-of-cocaine-seeking
#11
Kyle T Brown, Sophia C Levis, Casey E O'Neill, Alexis L Northcutt, Timothy J Fabisiak, Linda R Watkins, Ryan K Bachtell
Cocaine addiction is a chronic relapsing disorder characterized by persistent perturbations to an organism's homeostatic processes that result in maladaptive drug seeking. Although considerable attention has been directed at the consequences of neuronal changes following chronic cocaine taking, few studies have examined the role of microglia, the brain's resident immune cells, following chronic cocaine administration. Toll-Like Receptor 4 (TLR4) is a molecular pattern receptor that recognizes pathogens, danger signals, and xenobiotics and induces proinflammatory signaling in the central nervous system...
August 13, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28813452/plasma-metabolomics-reveals-membrane-lipids-aspartate-asparagine-and-nucleotide-metabolism-pathway-differences-associated-with-chloroquine-resistance-in-plasmodium-vivax-malaria
#12
Karan Uppal, Jorge L Salinas, Wuelton M Monteiro, Fernando Val, Regina J Cordy, Ken Liu, Gisely C Melo, Andre M Siqueira, Belisa Magalhaes, Mary R Galinski, Marcus V G Lacerda, Dean P Jones
BACKGROUND: Chloroquine (CQ) is the main anti-schizontocidal drug used in the treatment of uncomplicated malaria caused by Plasmodium vivax. Chloroquine resistant P. vivax (PvCR) malaria in the Western Pacific region, Asia and in the Americas indicates a need for biomarkers of resistance to improve therapy and enhance understanding of the mechanisms associated with PvCR. In this study, we compared plasma metabolic profiles of P. vivax malaria patients with PvCR and chloroquine sensitive parasites before treatment to identify potential molecular markers of chloroquine resistance...
2017: PloS One
https://www.readbyqxmd.com/read/28810137/time-gated-luminescence-imaging-of-singlet-oxygen-photoinduced-by-fluoroquinolones-and-functionalized-graphenes-in-daphnia-magna
#13
Tianlie Luo, Jingwen Chen, Bo Song, Hua Ma, Zhiqiang Fu, Willie J G M Peijnenburg
Singlet oxygen ((1)O2) can be photogenerated by photoactive xenobiotics and is capable of causing adverse effects due to its electrophilicity and its high reactivity with biological molecules. Detection of the production and distribution of (1)O2 in living organisms is therefore of great importance. In this study, a luminescent probe ATTA-Eu(3+) combined with time-gated luminescence imaging was adopted to detect the distribution and temporal variation of (1)O2 photoinduced by fluoroquinolone antibiotics and carboxylated/aminated graphenes in Daphnia magna...
July 29, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28807920/mediator-tail-module-is-required-for-tac1-activated-cdr1-expression-and-azole-resistance-in-candida-albicans
#14
Zhongle Liu, Lawrence C Myers
The human fungal pathogen Candida albicans develops drug resistance after long-term exposure to azole drugs in the treatment of chronic candidiasis. Gain-of-function (GOF) mutations in the transcription factor Tac1, and the consequent expression of its targets, drug efflux pumps Cdr1 and Cdr2, are a common mechanism by which C. albicans acquires fluconazole resistance. The mechanism by which GOF mutations hyperactivate Tac1 is currently unknown. Here, we define a transcriptional activation domain (TAD) at the C-terminus of Tac1...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28806688/concentration-dependent-transcriptome-responses-of-zebrafish-embryos-after-exposure-to-cadmium-cobalt-and-copper
#15
Laura Sonnack, Thorsten Klawonn, Ralf Kriehuber, Henner Hollert, Christoph Schäfers, Martina Fenske
Environmental metals are known to cause harmful effects to fish of which many molecular mechanisms still require elucidation. Particularly concentration dependence of gene expression effects is unclear. Focusing on this matter, zebrafish embryo toxicity tests were used in combination with transcriptomics. Embryos were exposed to three concentrations of copper (CuSO4), cadmium (CdCl2) and cobalt (CoSO4) from just after fertilization until the end of the 48hpf pre- and 96hpf post-hatch stage. The RNA was then analyzed on Agilent's Zebrafish (V3, 4×44K) arrays...
August 2, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/28806569/metabolic-profiling-of-dehydrodiisoeugenol-using-xenobiotic-metabolomics
#16
Qian-Qian Lv, Xiao-Nan Yang, Dong-Mei Yan, Wei-Qing Liang, Hong-Ning Liu, Xiu-Wei Yang, Fei Li
Dehydrodiisoeugenol (DDIE), a representative and major benzofuran-type neolignan in Myristica fragrans Houtt., shows anti-inflammatory and anti-bacterial actions. In order to better understand its pharmacological properties, xenobiotic metabolomics was used to determine the metabolic map of DDIE and its influence on endogenous metabolites. Total thirteen metabolites of DDIE were identified through in vivo and in vitro metabolism, and seven of them were reported for the first time in the present study. The identity of DDIE metabolites was achieved by comparison of the MS/MS fragmentation pattern with DDIE using ultra-performance chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI- QTOFMS)...
July 31, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28803989/mdr65-decreases-toxicity-of-multiple-insecticides-in-drosophila-melanogaster
#17
Haina Sun, Nicolas Buchon, Jeffrey G Scott
ABC transporters are ubiquitous membrane-bound proteins, present in both prokaryotes and eukaryotes. The major function of eukaryotic ABC transporters is to mediate the efflux of a variety of substrates (including xenobiotics) out of cells. ABC transporters have been widely investigated in humans, particularly for their involvement in multidrug resistance (MDR). Considerably less is known about their roles in transport and/or excretion in insects. ABC transporters are only known to function as exporters in insects...
August 10, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28803983/molecular-structure-of-a-prostaglandin-d-synthase-requiring-glutathione-from-the-brown-planthopper-nilaparvata-lugens
#18
Kohji Yamamoto, Akifumi Higashiura, Mamoru Suzuki, Kosuke Aritake, Yoshihiro Urade, Atsushi Nakagawa
Prostaglandins are involved in many physiological processes, and prostaglandin synthases facilitate the detoxification of xenobiotics as well as endogenous compounds, such as through glutathione conjugation. Specifically, prostaglandin D synthase (PGDS) catalyzes the isomerization of PGH2 to PGD2. Here we report the identification and structural analysis of PGDS from the brown planthopper rice pest Nilaparvata lugens (nlPGDS), which belongs to the sigma-class glutathione transferases. The structure of nlPGDS in complex with glutathione was determined at a resolution of 2...
August 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28803404/polymorphisms-in-xrcc1-ercc2-and-ercc3-dna-repair-genes-cyp1a1-xenobiotic-metabolism-gene-and-tobacco-are-associated-with-bladder-cancer-susceptibility-in-tunisian-population
#19
Molka Feki-Tounsi, Rim Khlifi, Ibtihel Louati, Mohamed Fourati, Mohamed-Nabil Mhiri, Amel Hamza-Chaffai, Ahmed Rebai
Other than the established environmental risk factors associated with bladder cancer (BC), little is known about the genetic variations determining the individual susceptibility of this complex disease. This study aimed to investigate the relationship of BC with environmental agents and polymorphisms in XRCC1, ERCC2, and ERCC3 DNA repair genes and CYP1A1, CYP2D6, NAT1, and NAT2 xenobiotic metabolism genes through a hospital-based case-control study in Tunisia. The selection of the single nucleotide polymorphisms (SNPs) (rs25487, rs 13181, rs415407, rs446421, rs1058172, rs4921880, and rs1208) was performed using the dbSNP database...
August 12, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28800408/effects-of-phenanthrene-on-early-development-of-the-pacific-oyster-crassostrea-gigas-thunberg-1789
#20
Diego J Nogueira, Jacó J Mattos, Patrick R Dybas, Fabrıcio Flores-Nunes, Silvio Tarou Sasaki, Satie Taniguchi, Éder C Schmidt, Zenilda L Bouzon, Márcia C Bícego, Claudio M R Melo, Guilherme Toledo-Silva, Afonso C D Bainy
Phenanthnere (PHE) is a polycyclic aromatic hydrocarbon continuously discarded in the marine environment and bioavailable to many aquatic species. Although studies about PHE toxicity have been documented for adult oysters, the effects on early developmental stages are poorly characterized in bivalves. In this study, the effects of PHE (0.02 and 2.0μg.L(-1)) were evaluated on the embryogenesis and larval development of Crassostrea gigas. Toxicity bioassays, growth and deformities assessment, analysis of shell calcium abundance and transcript levels of genes related to xenobiotic biotransformation (CYP2AU2, CYP30C1), immune system (Cg-Tal) and tissue growth and shell formation (Ferritin, Insulin-like, Cg-Try, Calmodulin and Nacrein) were assayed in D-shape larvae after 24h of PHE exposure...
August 1, 2017: Aquatic Toxicology
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