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Gabrielle do Amaral E Silva Müller, Karim Hahn Lüchmann, Guilherme Razzera, Guilherme Toledo-Silva, Maria João Bebianno, Maria Risoleta Freire Marques, Afonso Celso Dias Bainy
Diesel fuel water-accommodated fraction (diesel-WAF) is a complex mixture of organic compounds that may cause harmful effects to marine invertebrates. Expression of microsomal proteins can be changed by oil exposure, causing functional alterations in endoplasmic reticulum (ER). The aim of this study was to investigate changes in protein expression signatures in microsomes of oysterl Crassostrea brasiliana (=C.gasar) gill after exposure to 10% diesel-WAF for 24 and 72 h. Protein expression signatures of gills of oysters exposed to diesel-WAF were compared to those of unexposed oysters using two-dimensional electrophoresis (2-DE) to identify differentially expressed proteins...
June 6, 2018: Aquatic Toxicology
Karine Mazmanian, Todor Dudev, Carmay Lim
Hydrogen bonds to metal-ligands in proteins play a vital role in biological function. They help to stabilize/protect the metal complex and enhance metal-binding affinity/specificity, enzyme-substrate recognition, and enzyme activation. Yet, knowledge of the preferred hydrogen-bonding partners of metal ligands in different metalloproteins is lacking. Using well-calibrated methods, we have determined the preferred hydrogen-bonding partners of Cys- bound to native Zn2+ or xenobiotic Cd2+ in Zn-fingers of varying net charge and solvent accessibility as well as the key factors underlying the observed preference...
June 15, 2018: Inorganic Chemistry
Azhwar Raghunath, Ekambaram Perumal
The versatility offered by zebrafish (Danio rerio) makes it a powerful and an attractive vertebrate model in developmental toxicity and teratogenicity assays. Apart from the newly introduced chemicals as drugs, xenobiotics also induce abnormal developmental abnormalities and congenital malformations in living organisms. Over the recent decades, zebrafish embryo/larva has emerged as a potential tool to test teratogenicity potential of these chemicals. Zebrafish responds to compounds as mammals do as they share similarities in their development, metabolism, physiology, and signaling pathways with that of mammals...
2018: Methods in Molecular Biology
Hariz Islas-Flores, Itzayana Pérez-Alvaréz, Leobardo M Gómez-Oliván
Pharmaceuticals are chemical compounds which are used to preserve human and animal health. Once administered, these compounds are metabolized or can remain unaltered until excreted. Therefore, a mixture of pharmaceuticals and their metabolites enters municipal sewers and wastewater treatment plants where, depending on their polarity, water solubility, and persistence, they cannot be completely removed or transformed during the treatment process, so that unaltered pharmaceuticals and/or their metabolites can enter surface water...
2018: Methods in Molecular Biology
Celia N Sanchez-Dominguez, Hugo L Gallardo-Blanco, Mauricio A Salinas-Santander, Rocio Ortiz-Lopez
Biotransformation is an enzyme-catalyzed process in which the body converts endogenous compounds, xenobiotics and toxic substances into harmless or easily excreted metabolites. The biotransformation reactions are classified as phase I and II reactions. Uridine 5'-diphospho (UDP)-glucuronosyltransferases (UGTs) are a superfamily of phase II enzymes which have roles in the conjugation of xenobiotics or endogenous compounds, including drugs and bilirubin, with glucuronic acid to make them easier to excrete. The method the human body uses to achieve glucuronidation may be affected by a large interindividual variation due to changes in the sequences of the genes encoding these enzymes...
July 2018: Experimental and Therapeutic Medicine
Young Bok Abraham Kang, Jinsu Eo, Safak Mert, Martin L Yarmush, O Berk Usta
An important number of healthy and diseased tissues shows spatial variations in their metabolic capacities across the tissue. The liver is a prime example of such heterogeneity where the gradual changes in various metabolic activities across the liver sinusoid is termed as "zonation" of the liver. Here, we introduce the Metabolic Patterning on a Chip (MPOC) platform capable of dynamically creating metabolic patterns across the length of a microchamber of liver tissue via actively enforced gradients of various metabolic modulators such as hormones and inducers...
June 12, 2018: Scientific Reports
Taiki Abe, Yuto Amaike, Ryota Shizu, Miki Takahashi, Makoto Kano, Takuomi Hosaka, Takamitsu Sasaki, Susumu Kodama, Atsushi Matsuzawa, Kouichi Yoshinari
Constitutive androstane receptor (CAR) is a xenobiotic-responsive nuclear receptor that is highly expressed in the liver. CAR activation induces hepatocyte proliferation and hepatocarcinogenesis in rodents, but the mechanisms remain unclear. In this study, we investigated the association of CAR-dependent cell proliferation with Yes-associated protein (YAP), which is a transcriptional cofactor controlling organ size and cell growth through the interaction with various transcriptional factors including TEAD. In mouse livers, TCPOBOP (a mouse CAR activator) treatment increased the nuclear YAP accumulation and mRNA levels of YAP target genes as well as cell-cycle related genes along with liver hypertrophy and verteporfin (an inhibitor of YAP/TEAD interaction) cotreatment tended to attenuate them...
June 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Debabrata Mahapatra, Jill A Franzosa, Kyle Roell, Melaine Agnes Kuenemann, Keith A Houck, David M Reif, Denis Fourches, Seth W Kullman
High throughput screening (HTS) programs have demonstrated that the Vitamin D receptor (VDR) is activated and/or antagonized by a wide range of structurally diverse chemicals. In this study, we examined the Tox21 qHTS data set generated against VDR for reproducibility and concordance and elucidated functional insights into VDR-xenobiotic interactions. Twenty-one potential VDR agonists and 19 VDR antagonists were identified from a subset of >400 compounds with putative VDR activity and examined for VDR functionality utilizing select orthogonal assays...
June 11, 2018: Scientific Reports
Zhiguo Su, Tianjiao Dai, Yushi Tang, Yile Tao, Bei Huang, Qinglin Mu, Donghui Wen
Coastal ecosystem structures and functions are changing under natural and anthropogenic influences. In this study, surface sediment samples were collected from disturbed zone (DZ), near estuary zone (NEZ), and far estuary zone (FEZ) of Hangzhou Bay, one of the most seriously polluted bays in China. The bacterial community structures and predicted functions varied significantly in different zones. Firmicutes were found most abundantly in DZ, highlighting the impacts of anthropogenic activities. Sediment total phosphorus was most influential on the bacterial community structures...
June 2018: Marine Pollution Bulletin
Mithat Gunduz, Upendra A Argikar, Amanda L Cirello, Jennifer L Dumouchel
BACKGROUND: Acyl glucuronides of xenobiotics have been a subject of wide interest from the pharmaceutical industry with respect biochemical reactivity, hepatic disposition, and enterohepatic circulation. The reactivity and lack of stability of an acyl glucuronide for a clinical candidate could pose major developability concerns. To date, multiple in vitro assays have been published to assess the risk associated with acyl glucuronides. Despite this fact, the translation of these findings to predicting clinical safety remains poor...
June 10, 2018: Drug Metabolism Letters
Emine B Yalcin, Ming Tong, Gina Gallucci, Suzanne M de la Monte
BACKGROUND: The high levels of blood alcohol achieved with chronic plus binge alcohol exposures are somewhat reduced by co-administration of tobacco specific Nicotine-Derived Nitrosamine Ketone (NNK) suggesting that NNK may alter alcohol metabolism. OBJECTIVE: To test this hypothesis, we We examined ethanol and acetaldehyde-metabolizing enzyme activities and malondialdehyde adduct formation in rats exposed to ethanol (chronic + binge), NNK, or both. METHODS: 4-week old Long Evans rats were fed liquid diets containing 0% or 26% caloric ethanol for 8 weeks...
June 10, 2018: Drug Metabolism Letters
Shuqi Pu, Xiaojie Wu, Xiaoying Yang, Yunzhan Zhang, Yunkai Dai, Yueling Zhang, Xiaoting Wu, Yan Liu, Xiaona Cui, Haiyong Jin, Jianhong Cao, Ruliu Li, Jiazhong Cai, Qizhi Cao, Ling Hu, Yong Gao
Xenobiotic nuclear receptors (XNRs) are nuclear receptors that characterized by coordinately regulating the expression of genes encoding drug-metabolizing enzymes and transporters to essentially eliminate and detoxify xenobiotics and endobiotics from the body, including the peroxisome proliferator-activated receptor (PPAR), the farnesoid X receptor (FXR), the liver X receptor (LXR), the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). Heretofore, increasing evidences have suggested that these five XNRs are not only involved in the regulation of xeno-/endo-biotics detoxication but also the development of human diseases, such as cancer, obesity and diabetes...
June 10, 2018: Current Drug Metabolism
Jiao Liu, Xueyao Zhang, Haihua Wu, Yue Gao, Kristopher Silver, Enbo Ma, Jianzhen Zhang, Kun Yan Zhu
Cytochrome P450 monooxygenases (P450s) are important enzymes for biotransformations of various endogenous and xenobiotic substances in various organisms. In this study, we examined microsomal P450 protein content and enzymatic activity in four major detoxification tissues dissected from fifth-instar nymphs of the migratory locust (Locusta migratoria). The highest microsomal P450 protein content was found in the gastric caeca (a part of the midgut), followed by the midgut, Malpighian tubules and fat bodies. Microsomal P450s showed the highest aromatic hydroxylation, O-dealkylation and O-dearylation activities towards six of the seven model substrates examined in the fat bodies...
May 30, 2018: Chemosphere
Antonia Youssef, Anne von Koschembahr, Sylvain Caillat, Sebastien Corre, Marie-Dominique Galibert, Thierry Douki
Exposure to solar UV is at the origin of numerous photodegradation pathways in biomolecules. Tryptophan is readily modified by UVB radiation into ring-opened and oxidized photoproducts. One of them, 6-formylindolo[3,2-b]carbazole (FICZ), has been extensively studied in the recent years because it very efficiently binds to AhR, a major factor in numerous biological processes, such as metabolism of xenobiotics. Unfortunately, little information is available on the actual yield of FICZ upon exposure to low and biologically relevant doses of UV radiation...
June 8, 2018: Photochemistry and Photobiology
Jim Reed, Scott A Wetzel
The activation and differentiation of CD4+ T cells play a critical role in establishing and subsequently controlling protective adaptive immune responses. Flow cytometry is a powerful technique with which to assess the potential of xenobiotics to influence CD4+ T cell activation and differentiation. With flow cytometry, cells are stained with fluorochrome-conjugated antibodies and/or specific fluorescent probes to assess T cell activation, proliferation, effector cytokine production, and transcription factor expression...
2018: Methods in Molecular Biology
Jennifer Franko, Jamie L McCall, John B Barnett
Macrophages are a heterogeneous group of cells that have a multitude of functions depending on their differentiation state. While classically known for their phagocytic and antigen presentation abilities, it is now evident that these cells fulfill homeostatic functions beyond the elimination of invading pathogens. In addition, macrophages have also been implicated in the downregulation of inflammatory responses following pathogen removal, tissue remodeling, repair, and angiogenesis. Alterations in macrophage differentiation and/or activity due to xenobiotic exposure can have grave consequences on organismal homeostasis, potentially contributing to disease due to immunosuppression or chronic inflammatory responses, depending upon the pathways affected...
2018: Methods in Molecular Biology
Scott T Espenschied, Robert M Tighe, Kymberly M Gowdy
Assessing the immunotoxicity of xenobiotics by current regulatory testing has revealed compounds that can cause immunosuppression and stimulation. Flow cytometry is a cutting edge technique that can provide data on how toxicants can alter the quality and quantity of the immune response after exposure. Here we describe protocols for how to use flow cytometry to measure the immune response in multiple rodent organs (blood and lymphoid and nonlymphoid) as well as in novel models recently being utilized in the field of toxicology...
2018: Methods in Molecular Biology
Gregory S Ladics
The sheep erythrocyte T-dependent antibody response (TDAR) evaluates the ability of animals sensitized in vivo to produce primary IgM antibodies to sheep erythrocytes (sRBC). The assay enumerates the number of antigen-specific IgM antibody-producing cells in the spleen. When exposure to the test material takes place in vivo, as does sensitization, the actual quantification of the number of antibody-producing cells occurs ex vivo. Following the animal being euthanized, a single-cell suspension of spleen cells is prepared...
2018: Methods in Molecular Biology
Jingjing Jiao, Gordon P Watt, Heather L Stevenson, Tiffany L Calderone, Susan P Fisher-Hoch, Yuanqing Ye, Xifeng Wu, John M Vierling, Laura Beretta
Telomerase reverse transcriptase ( TERT ) mutation is the most frequent genetic alteration in hepatocellular carcinoma (HCC). Our aims were to investigate whether TERT mutations can be detected in circulating cell-free DNA (cfDNA) of patients with HCC and/or cirrhosis and characterize clinical parameters associated with these mutations. We retrieved data on TERT C228T and C250T promoter mutations in 196 HCCs from The Cancer Genome Atlas. We measured these TERT mutations in plasma cfDNA in 218 patients with HCC and 81 patients with cirrhosis without imaging evidence of HCC...
June 2018: Hepatology Communications
Sonia Chadha, Sayaji T Mehetre, Ravindra Bansal, Alan Kuo, Andrea Aerts, Igor V Grigoriev, Irina S Druzhinina, Prasun K Mukherjee
Background: Cytochrome P450s form an important group of enzymes involved in xenobiotics degradation and metabolism, both primary and secondary. These enzymes are also useful in industry as biotechnological tools for bioconversion and a few are reported to be involved in pathogenicity. Trichoderma spp. are widely used in industry and agriculture and are known for their biosynthetic potential of a large number of secondary metabolites. For realising the full biosynthetic potential of an organism, it is important to do a genome-wide annotation and cataloguing of these enzymes...
2018: Fungal Biology and Biotechnology
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