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liver detoxification

Danica E DeGroot, Adam Swank, Russell S Thomas, Mark Strynar, Mi-Young Lee, Paul L Carmichael, Steven O Simmons
The US EPA's ToxCast program is designed to assess chemical perturbations of molecular and cellular endpoints using a variety of high-throughput screening (HTS) assays. However, existing HTS assays have limited or no xenobiotic metabolism which could lead to false positive (chemical is detoxified in vivo) as well as false negative results (chemical is bioactivated in vivo) and thus potential mischaracterization of chemical hazard. To address this challenge, the ten most prevalent human liver cytochrome P450 (CYP) enzymes were introduced into a human cell line (HEK293T) with low endogenous metabolic capacity...
March 16, 2018: Journal of Pharmacological and Toxicological Methods
Carole Mast, Dominique Dardevet, Isabelle Papet
The optimisation of nutritional support for the growing number of older individuals does not usually take into account medication. Paracetamol (acetaminophen; APAP) is the first intention treatment of chronic pain that is highly prevalent and persistent in the elderly. Detoxification of APAP occurs in the liver and utilises sulfate and glutathione (GSH), both of which are issued from cysteine (Cys), a conditionally indispensable amino acid. The detoxification-induced siphoning of Cys could reduce the availability of Cys for skeletal muscle...
March 20, 2018: Nutrition Research Reviews
Mayada R Farag, Mahmoud Alagawany, Mohamed M Badr, Samah R Khalil, Mohamed S El-Kholy
The present study was carried out to investigate the toxic effects of dietary inclusion of raw Jatropha cucas meal [RJM, 3.5%] on productive and reproductive performances of laying Japanese quail and the influence of physical treatment of jatropha meal by heating at [100o c] for 24 or 48 h [JH24 or JH48 respectively] on reducing these effects. The inclusion of RJM in quail diets significantly decreased the egg production, fertility and hatchability percentages and resulted in a high mortality rate. While heat-treated jatropha meal [JH24 or JH48 ] improved such undesirable effects...
March 12, 2018: Theriogenology
Joseph Ashley Kirkly, Gretchen K Bielmyer-Fraser, John F Elder, David L Bechler
This study examines the microgeographic structure of the Alapahoochee watershed, part of the Suwannee River basin, south-central GA, USA, and relates it to variations in liver metal concentrations and genetic structure of the Florida cottonmouth, Agkistrodon piscivorus conanti. One objective was to determine if liver metal concentrations in A. piscivorus differ between Grand Bay and Mud creeks, which form the watershed's upper portion. Grand Bay Creek is relatively pristine, whereas Mud Creek is polluted with various metals...
March 15, 2018: Environmental Monitoring and Assessment
Sarva Mangala Praveena, Seoh Wei Teh, Ranjith Kumar Rajendran, Narayanan Kannan, Chu-Ching Lin, Rozaini Abdullah, Suresh Kumar
Phthalates have been blended in various compositions as plasticizers worldwide for a variety of purposes. Consequently, humans are exposed to a wide spectrum of phthalates that needs to be researched and understood correctly. The goal of this review is to focus on phthalate's internal exposure pathways and possible role of human digestion on liver toxicity. In addition, special focus was made on stem cell therapy in reverting liver toxicity. The known entry of higher molecular weight phthalates is through ingestion while inhalation and dermal pathways are for lower molecular weight phthalates...
March 15, 2018: Environmental Science and Pollution Research International
A C Van Erp, R A Rebolledo, D Hoeksma, N R Jespersen, P J Ottens, R Nørregaard, M Pedersen, C Laustsen, J G M Burgerhof, J C Wolters, J Ciapaite, H E Bøtker, H G D Leuvenink, B Jespersen
Hepatic and renal energy status prior to transplantation correlates with graft survival. However, effects of brain death (BD) on organ-specific energy status are largely unknown. We studied metabolism, perfusion, oxygen consumption, and mitochondrial function in the liver and kidneys following BD. BD was induced in mechanically-ventilated rats, inflating an epidurally-placed Fogarty-catheter, with sham-operated rats as controls. A 9.4T-preclinical MRI system measured hourly oxygen availability (BOLD-related R2*) and perfusion (T1-weighted)...
March 13, 2018: Scientific Reports
Ingrid Kratzer, Nathalie Strazielle, Elodie Saudrais, Kati Mönkkönen, Céline Maleval, Sandrine Blondel, Jean-François Ghersi-Egea
Exposure of the developing brain to toxins, drugs, or deleterious endogenous compounds during the perinatal period can trigger alterations in cell division, migration, differentiation, and synaptogenesis, leading to life-long neurological impairment. The brain is protected by cellular barriers acting through multiple mechanisms, some of which are still poorly explored. We used a combination of enzymatic assays, live tissue fluorescence microscopy, and an in vitro cellular model of the blood-CSF barrier to investigate an enzymatic detoxification pathway in the developing male and female rat brain...
March 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Joana Carrola, Ricardo J B Pinto, Maryam Nasirpour, Carmen S R Freire, Ana M Gil, Conceição Santos, Helena Oliveira, Iola F Duarte
The expansion of biomedical and therapeutic applications of silver nanoparticles (AgNPs) raises the need to further understand their biological effects on human cells. In this work, NMR metabolomics has been applied to reveal the metabolic effects of AgNPs toward human hepatoma (HepG2) cells, which are relevant with respect to nanoparticle accumulation and detoxification. Cellular responses to widely disseminated citrate-coated AgNPs (Cit30) and to emergent biogenic AgNPs prepared using an aqueous plant extract as reducing and stabilizing agent (GS30) have been compared with a view to assess the influence of nanoparticle coating on the metabolic effects produced...
March 9, 2018: Journal of Proteome Research
Raphaël Cornu, Nathalie Rougier, Yann Pellequer, Alf Lamprecht, Paul Hamon, Ruoya Li, Arnaud Beduneau, Hélène Martin
Nanomedicines represent a promising approach in the treatment and diagnosis of numerous disorders. The majority of the injected dose of nanoparticles (NPs) is sequestrated in the liver. Despite this hepatic tropism, the interaction of NPs with the detoxification function of the liver remains unclear. The present study consists of evaluating the impact of biodegradable poly(lactide-co-glycolide) (PLGA) and silica NPs on cytochrome P450 (CYP) activities. The effects of NPs were evaluated in vitro on human and rat hepatocytes in primary cultures and in vivo by intravenous injections in healthy rats...
March 1, 2018: Nanoscale
Denise Damasceno Guerreiro, Laritza Ferreira de Lima, Gildas Tetaping Mbemya, Carolina Mielgo Maside, André Marrocos Miranda, Kaio César Simiano Tavares, Benner Geraldo Alves, Luciana Rocha Faustino, Johan Smitz, José Ricardo de Figueiredo, Ana Paula Ribeiro Rodrigues
The multidrug resistance proteins ABCB1, ABCC2 and ABCG2 are an energy-dependent efflux pump that functions in systemic detoxification processes. Physiologically expressed in a variety of tissues, most abundantly in the liver and intestinal epithelia, placenta, blood-brain barrier and various stem cells, until now, these pumps were not identified in goat ovarian tissue. Therefore, the aim of this study is to analyze ABCB1, ABCC2, and ABCG2 mRNA and protein expression in goat preantral follicles. Fragments (3 × 3 × 1 mm) from five pairs of ovary (n = 10) obtained from five goat were collected and immediately submitted to qPCR, Western blot, and immunofluorescence assay for mRNA detection and identification and localization of the ABC transporters, respectively...
February 27, 2018: Cell and Tissue Research
Eita Sasaki, Tsuyoshi Yokoi
Several drugs have been withdrawn from the market or restricted to avoid unexpected adverse outcomes. Drug-induced liver injury (DILI) is a serious issue for drug development. Among DILIs, idiosyncratic DILIs have been a serious problem in drug development and clinical uses. Idiosyncratic DILI is most often unrelated to pharmacological effects or the dosing amount of a drug. The number of drugs that cause idiosyncratic DILI continue to grow in part because no practical preclinical tests have emerged that can identify drug candidates with the potential for developing idiosyncratic DILIs...
2018: Journal of Toxicological Sciences
Rachid Jellali, Perrine Zeller, Françoise Gilard, Audrey Legendre, Marie José Fleury, Sébastien Jacques, Guillaume Tcherkez, Eric Leclerc
Dichlorodiphenyl-trichloroethane (DDT) and permethrin (PMT) are amongst most prevalent pesticides in the environment. Although their toxicity has been extensively studied, molecular mechanisms and metabolic effects remain unclear, including in liver where their detoxification occurs. Here, we used metabolomics, coupled to RT-qPCR analysis, to examine effects of DDT and PMT on hepatocytes cultivated in biochips. At 150 μM, DDT caused cell death, cytochrome P450 induction and modulation of estrogen metabolism...
February 10, 2018: Environmental Toxicology and Pharmacology
Shuang Bao, Xiangping Nie, Yang Liu, Chao Wang, Sijia Liu
As a widely used lipid lowering agent, simvastatin recently has been frequently detected in aquatic environment and the potential adverse effects from simvastatin exposure to non-target organisms such as fish is worthy of more attention. The aim of this study was to reveal the responses of detoxification system in fish to simvastatin exposure. In this investigation a ubiquitous small freshwater fish, mosquito fish (Gambusia affinis), was employed as test organism, and the transcriptional expression of nucleus transcriptional factor pregnane X receptor (PXR) and its downstream genes, including P-glycoprotein (P-gp), cytochrome 3A (CYP3A), multidrug resistance protein 2 (MRP2), UDP-glucuronosyl transferase (UGT) in mosquito fish were investigated by qRT-PCR methods under the exposure of concentrations of simvastatin (0...
February 21, 2018: Ecotoxicology and Environmental Safety
Sayaka Matsumoto, Junichi Kikuta, Masaru Ishii
The liver is a vital organ in the body. It has various essential functions, including detoxification, protein synthesis, and control of infection. Because of its medical importance, liver diseases such as hepatitis and cirrhosis can be crucial for an individual. Exploring dynamics of living cells in the liver would provide the clues for understanding the pathology. However, due to its technical difficulty, few studies have used intravital liver imaging. To resolve this, we have established a novel imaging system for visualizing liver cell dynamics in living animals...
2018: Methods in Molecular Biology
A Santos, F J Giráldez, E Trevisi, L Lucini, J Frutos, S Andrés
The increasing world population is driving demand for improved efficiency of feed resources of livestock. However, the molecular mechanisms behind various feed efficiency traits and their regulation by nutrition remain poorly understood. Here we aimed to identify differentially expressed (DE) genes in the liver tissues of fattening Merino lambs and differences in metabolites accumulated in plasma to identify modified metabolic pathways as a consequence of milk restriction during the suckling period. Twenty-four male Merino lambs (4...
February 19, 2018: Journal of Animal Science
Rachel J Eclov, Mee J Kim, Robin P Smith, Nadav Ahituv, Deanna L Kroetz
ABCG2 encodes the breast cancer resistance protein (BCRP), an efflux membrane transporter important in detoxification of xenobiotics. In the present study, the basal activity of the ABCG2 promoter in liver, kidney, intestine and breast cell lines was examined using luciferase reporter assays. The promoter activity of reference and variant ABCG2 sequences were compared in HepG2, HEK293T, HCT116 and MCF-7 cell lines. The ABCG2 promoter activity was strongest in the kidney and intestine cell lines. Four variants in the basal ABCG2 promoter (rs76656413, rs66664036, rs139256004 and rs59370292) decreased the promoter activity by 25-50% in at least three of the four cell lines...
February 21, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Adrien Labriet, Eric P Allain, Michele Rouleau, Yannick Audet-Delage, Lyne Villeneuve, Chantal Guillemette
The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics. Preferred substrates possess tertiary aliphatic amines and heterocyclic amines such as tobacco carcinogens and several anti-depressants and anti-psychotics. We hypothesized that alternative splicing (AS) constitutes a mean to regulate steady state levels of UGT2B10 and enzyme activity. We established the transcriptome of UGT2B10 in normal and tumoral tissues of multiple individuals...
February 9, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Carlos Gaspar, Jonás I Silva-Marrero, María C Salgado, Isabel V Baanante, Isidoro Metón
Glutamate dehydrogenase (Gdh) plays a central role in ammonia detoxification by catalysing reversible oxidative deamination of L-glutamate into α-ketoglutarate using NAD+ or NADP+ as cofactor. To gain insight into transcriptional regulation of glud, the gene that codes for Gdh, we isolated and characterised the 5' flanking region of glud from gilthead sea bream (Sparus aurata). In addition, tissue distribution, the effect of starvation as well as short- and long-term refeeding on Gdh mRNA levels in the liver of S...
February 8, 2018: Journal of Molecular Endocrinology
Husna Yetti, Hisao Naito, Yuan Yuan, Xiaofang Jia, Yumi Hayashi, Hazuki Tamada, Kazuya Kitamori, Katsumi Ikeda, Yukio Yamori, Tamie Nakajima
During middle age, women are less susceptible to nonalcoholic steatohepatitis (NASH) than men. Thus, we investigated the underlying molecular mechanisms behind these sexual differences using an established rat model of NASH. Mature female and male stroke-prone spontaneously hypertensive 5/Dmcr rats were fed control or high-fat-cholesterol (HFC) diets for 2, 8, and 14 weeks. Although HFC-induced hepatic fibrosis was markedly less severe in females than in males, only minor gender differences were observed in expression levels of cytochrome P450 enzymes (CYP)7A1, CYP8B1 CYP27A1, and CYP7B1, and multidrug resistance-associated protein 3, and bile salt export pump, which are involved in fibrosis-related bile acid (BA) kinetics...
2018: PloS One
Mayara Pereira Neves, João Paulo de Arruda Amorim, Rosilene Luciana Delariva
This study aimed to evaluate the histopathological biomarkers of the gills and liver of endemic catfish to test the hypothesis that, in environments under intense land use by agricultural activities, histopathological alterations occur more severely. Samples were collected by electrofishing in seven streams in the Lower Iguaçu basin quarterly from August 2015 to February 2016. The gills and livers were processed according to routine histological methods and examined by light microscopy. The histopathological alterations observed in fish from the streams with a higher percentage of natural vegetation cover were considered modest and indicated normal functioning of the organ (such as edema, hyperplasia, and leukocyte infiltration)...
February 12, 2018: Environmental Science and Pollution Research International
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