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drug induced liver toxicity

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https://www.readbyqxmd.com/read/28646742/image-analysis-for-tsh-mrna-in-situ-hybridization-in-pituitary-glands-from-rats-with-thyroid-follicular-cell-hypertrophy-after-treatment-with-three-different-test-compounds
#1
Juergen Funk, Martin Ebeling, Thomas Singer, Christian Landes
The goal of this in situ hybridization and image analysis technique is to study the effects of new pharmacological/chemical entities on the thyroid and pituitary gland in rats, reveal the pathogenesis of thyroid follicular cell hypertrophy and to retrospectively exclude the risk of thyroid tumor development in humans. In the present study, we describe the increase of thyroid-stimulating hormone- (TSH-) beta subunit mRNA in the pars distalis of the pituitary gland and the quantitative measurement of TSH mRNA positive cells from rats of three 4-week toxicity studies treated with three different test compounds inducing thyroid follicular cell and hepatocellular hypertrophy in rats...
June 11, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28645576/mechanisms-of-hepatocellular-toxicity-associated-with-new-psychoactive-synthetic-cathinones
#2
Dino Luethi, Matthias E Liechti, Stephan Krähenbühl
Synthetic cathinones are a new class of psychostimulant substances. Rarely, they can cause liver injury but associated mechanisms are not completely elucidated. In order to increase our knowledge about mechanisms of hepatotoxicity, we investigated the effect of five frequently used cathinones on two human cell lines. Bupropion was included as structurally related drug used therapeutically. In HepG2 cells, bupropion, MDPV, mephedrone and naphyrone depleted the cellular ATP content at lower concentrations (0...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28638868/in-vivo-effect-of-ruta-chalepensis-extract-on-hepatic-cytochrome-3a1-in-rats
#3
Edith Fabiola Martínez-Pérez, Fernando Hernández-Terán, Luis Benjamín Serrano-Gallardo
BACKGROUND: Since the time when drugs began to be used, it became evident that they could produce a therapeutic effect, but also a clinical condition of toxicity or no effect at all on humans, despite using the same doses in different patients. Such untoward effects were termed "drug idiosyncrasy" and also "idiosyncratic drug effects", but the factors producing such diverse responses were never taken into account. MATERIALS AND METHODS: Ruta chalepensis L. (fringed rue) is an herbaceous plant of the Rutaceae family used in traditional medicine due to its properties, such as its analgesic and antipyretic effects...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28636309/quantitative-chemical-proteomic-profiling-of-the-in-vivo-targets-of-reactive-drug-metabolites
#4
Landon R Whitby, R Scott Obach, Gabriel M Simon, Matthew M Hayward, Benjamin F Cravatt
Idiosyncratic liver toxicity represents an important problem in drug research and pharmacotherapy. Reactive drug metabolites that modify proteins are thought to be a principal factor in drug-induced liver injury. Here, we describe a quantitative chemical proteomic method to identify the targets of reactive drug metabolites in vivo. Treating mice with clickable analogues of four representative hepatotoxic drugs, we demonstrate extensive covalent binding that is confined primarily to the liver. Each drug exhibited a distinct target profile that, in certain cases, showed strong enrichment for specific metabolic pathways (e...
June 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28633424/three-dimensional-3d-heparg-spheroid-model-with-physiologically-relevant-xenobiotic-metabolism-competence-and-hepatocyte-functionality-for-liver-toxicity-screening
#5
Sreenivasa C Ramaiahgari, Suramya Waidyanatha, Darlene Dixon, Michael J DeVito, Richard S Paules, Stephen S Ferguson
Effective prediction of human responses to chemical and drug exposure is of critical importance in environmental toxicology research and drug development. While significant progress has been made to address this challenge using in vitro liver models, these approaches often fail due to inadequate tissue model functionality. Herein, we describe the development, optimization, and characterization of a novel three-dimensional (3D) spheroid model using differentiated HepaRG cells that achieve and maintain physiologically-relevant levels of xenobiotic metabolism (CYP1A2, CYP2B6, and CYP3A4/5)...
June 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28628229/troxerutin-with-copper-generates-oxidative-stress-in-cancer-cells-its-possible-chemotherapeutic-mechanism-against-hepatocellular-carcinoma
#6
A Subastri, A Suyavaran, Preedia Babu E, Nithyananthan S, R Bharathidasan, C Thirunavukkarasu
Troxerutin (TXER) a rutin derivative is known for its anticancer effect against hepatocellular carcinoma (HCC). As part of large study, recently we have shown TXER interact with genetic material and its anti-mutagenic property. In the present study we have explored its possible mode of action in HCC. Since TXER alone did not show significant anticancer effect on Huh-7 cells, in vitro biochemical assays were performed for determining anticancer efficacy of TXER + metal complex using transition metals such as Cu, Zn & Fe...
June 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28619387/evaluation-of-ameliorative-ability-of-silibinin-against-zidovudine-and-isoniazid-induced-hepatotoxicity-and-hyperlipidaemia-in-rats-role-of-silibinin-in-phase-i-and-ii-drug-metabolism
#7
Raghu Ramanathan, Karthikeyan Sivanesan
HIV/AIDS patients have suppressed immune system, making them vulnerable to many opportunistic infections including tuberculosis (TB). The patients who are co-infected with TB undergo combined regimens with anti-retroviral drugs such as zidovudine (AZT) and anti-tubercular drug such as isoniazid (INH) for therapy leading to hepatotoxicty. Silibinin (SBN), extracted from Silybum marianum commonly called as "Milk thistle" is used against several drugs-induced hepatotoxicity. The present study evaluates the ameliorative effect of SBN against AZT alone, INH alone, and INH + AZT-induced toxic insults to liver of rats...
June 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28618760/changes-in-the-serum-liver-and-renal-cortical-lipids-and-electrolytes-in-rabbits-with-cisplatin-induced-nephrotoxicity
#8
Abdelgayoum Ahmed Abdel-Gayoum, Mohamed Hamza Sulaiman Ahmida
BACKGROUND/AIM: Cisplatin is an anticancer drug that can induce nephrotoxicity. Its toxicity is associated with dyslipidemia and disturbed electrolyte balance. In the present study we investigated the changes in serum lipid profile and electrolyte levels and their contents in kidney and liver tissues of rabbits treated with cisplatin. MATERIALS AND METHODS: Twenty-eight adult male New Zealand White rabbits were used in the experiment. Animals of groups C, P1, and P2 were injected with saline, cisplatin (4...
June 12, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28615926/mechanistic-modelling-of-drug-induced-liver-injury-investigating-the-role-of-innate-immune-responses
#9
Lisl Km Shoda, Christina Battista, Scott Q Siler, David S Pisetsky, Paul B Watkins, Brett A Howell
Drug-induced liver injury (DILI) remains an adverse event of significant concern for drug development and marketed drugs, and the field would benefit from better tools to identify liver liabilities early in development and/or to mitigate potential DILI risk in otherwise promising drugs. DILIsym software takes a quantitative systems toxicology approach to represent DILI in pre-clinical species and in humans for the mechanistic investigation of liver toxicity. In addition to multiple intrinsic mechanisms of hepatocyte toxicity (ie, oxidative stress, bile acid accumulation, mitochondrial dysfunction), DILIsym includes the interaction between hepatocytes and cells of the innate immune response in the amplification of liver injury and in liver regeneration...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28612667/all-that-glitters-yellow-is-not-gold-presentation-and-pathophysiology-of-bile-cast-nephropathy
#10
Mitchell Pitlick, Prerna Rastogi
BACKGROUND: Acute kidney injury (AKI) often manifests in patients with liver disease because of a prerenal cause and presents as acute tubular necrosis or hepatorenal syndrome. Distinguishing between these entities is important for prognosis and treatment. Some patients may develop AKI related to their underlying liver disease: for example, membranoproliferative glomerulonephritis or IgA nephropathy. Bile cast nephropathy is an often ignored differential diagnosis of AKI in the setting of obstructive jaundice...
June 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28612092/involvement-of-cytochrome-p450-in-cisplatin-treatment-implications-for-toxicity
#11
REVIEW
Júlia Coelho França Quintanilha, Vanessa Marcilio de Sousa, Marília Berlofa Visacri, Laís Sampaio Amaral, Roseane Maria Maia Santos, Tomás Zambrano, Luis Antonio Salazar, Patricia Moriel
PURPOSE: The aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatin toxicity. METHODS: This article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatin toxicity. We performed a narrative mini-review. RESULTS: The studies review showed that CYP450 enzymes have an important role in drug-induced hepatotoxicity and nephrotoxicity, mainly CYP2E1 and CYP4A11. The studies also suggested that the cisplatin and CYP2E1 interaction leads to the generation of reactive oxygen species (ROS) and other oxidants resulting in renal injury; and that ROS generated by both the use of cisplatin and by the CYP2E1 increases tissue damage, induces apoptosis, and causes liver failure...
June 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28606603/identification-of-enzymes-responsible-for-nitrazepam-metabolism-and-toxicity-in-human
#12
Keigo Konishi, Tatsuki Fukami, Saki Gotoh, Miki Nakajima
Nitrazepam (NZP) is a hypnotic agent that rarely causes liver injuries in humans and teratogenicity in rodents. In humans, NZP is primarily metabolized to 7-aminonitrazepam (ANZP) by reduction and subsequently to 7-acetylamino nitrazepam (AANZP) by acetylation. ANZP can be regenerated from AANZP by hydrolysis in rodents, but it is still unclear whether this reaction occurs in humans. In rodents, AANZP may be associated with teratogenicity, while in humans, it is known that drug-induced liver injuries may be caused by NZP reactive metabolite(s)...
June 9, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28604124/test-systems-in-drug-discovery-for-hazard-identification-and-risk-assessment-of-human-drug-induced-liver-injury
#13
Richard J Weaver, Catherine Betts, Eric A G Blomme, Helga H J Gerets, Klaus Gjervig Jensen, Philip G Hewitt, Satu Juhila, Gilles Labbe, Michael J Liguori, Natalie Mesens, Monday O Ogese, Mikael Persson, Jan Snoeys, James L Stevens, Tracy Walker, B Kevin Park
Introduction The liver is an important target for drug-induced toxicities. Early detection of hepatotoxic drugs requires use of well-characterized test systems, yet current knowledge, gaps and limitations of tests employed remains an important issue for drug development. Areas Covered The current state of the science, understanding and application of test systems in use for the detection of drug-induced cytotoxicity, mitochondrial toxicity, cholestasis and inflammation is summarized. The test systems highlighted herein cover mostly in vitro and some in vivo models and endpoint measurements used in the assessment of small molecule toxic liabilities...
June 12, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28603418/vesicular-melatonin-efficiently-downregulates-sodium-fluoride-induced-rat-hepato-and-broncho-tnf-%C3%AE-tgf-%C3%AE-expressions-and-associated-oxidative-injury-a-comparative-study-of-liposomal-and-nanoencapsulated-forms
#14
Suvomoy Sana, Swarupa Ghosh, Nirmalendu Das, Sibani Sarkar, Ardhendu Kumar Mandal
The importance of fluoride as a natural and industrial toxicant is recognized worldwide. We evaluated the regulating role and biological effect of vesicular (liposomal and nanoencapsulated) melatonin (N-acetyl-5-methoxytryptamine) for drug delivery and controlled release on the depletion of inflammatory mediators, as well as oxidative damage in sodium fluoride (NaF)-treated lungs and liver. Hepatic and bronchial damage was induced in Swiss albino rats with a single acute ingestion of NaF (48 mg/kg body weight, oral gavage)...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28603116/anti-diabetic-and-hypolipidemic-effects-of-extract-from-the-seed-of-gossypium-herbaceum-l-in-alloxan-induced-diabetic-rabbits
#15
Rifat Uzzaman, Maida Ghaffar
Anti-diabetic and hypolipidemic effects of seed of Gossypium herbaceum L (GH) and its aqueous and ethanol extracts were investigated in alloxan-induced diabetic rabbits. Normal, Alloxan-induced diabetic and treated groups of rabbit were examined for their serum glucose, triglyceride, cholesterol, creatinine and urea levels. Water/food intake and toxic effect of test substances were also observed in treated rabbits. Effect of test agents on architecture of pancreatic β-cells was evaluated histopathologically in rabbits...
January 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28603042/mephedrone-exposure-in-adolescent-rats-alters-the-rewarding-effect-of-morphine-in-adults
#16
Listos Joanna, Talarek Sylwia, Gryzinska Magdalena, Listos Piotr, Kedzierska Ewa, Orzelska-Gorka Jolanta, Dylewska Malgorzata, Lupina Malgorzata, Jolanta H Kotlinska
An increasing number of data show that exposure to mephedrone in adolescence can have long-lasting implication on brain activity and on peripheral organs/tissues. The aim of this study was to investigate whether adolescent exposure to mephedrone (10mg/kg, i.p.) has influence upon the rewarding effect of morphine (5mg/kg, i.p.) in adult rats. Thus, the adolescent rats (on the 30th PND) were treated with mephedrone for 7 consecutive days. When the animals were adult (on the 60th PND) the morphine-induced conditioned place preference (CPP) test was performed...
June 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28587677/anti-obesity-activity-acute-toxicity-and-chemical-constituents-of-aqueous-and-ethanol-viola-mandshurica-extracts
#17
Yoon-Young Sung, Dong-Seon Kim, Seung-Hyung Kim, Ho Kyoung Kim
BACKGROUND: Viola mandshurica has traditionally been used as an expectorant, diuretic, and anti-inflammatory drug. The present study was designed to test the hypothesis that low doses of two different V. mandshurica extracts have anti-obesity effects. METHODS: We evaluated the effects of ethanol extract (VME) and aqueous extract (VMA) from V. mandshurica on high-fat diet (HFD)-induced obese mice as well as the acute oral toxicities and chemical compositions of both extracts...
June 6, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28580117/two-photon-fluorescent-probe-for-revealing-drug-induced-hepatotoxicity-via-mapping-fluctuation-of-peroxynitrite
#18
Yong Li, Xilei Xie, Xiu'e Yang, Mengmeng Li, Xiaoyun Jiao, Yuhui Sun, Xu Wang, Bo Tang
Drug-induced injury has attracted increasing attention in public health issues. Among them, hepatotoxicity has been regarded as the leading clinical problem caused by drug toxicity. However, owing to the complexity of the involved pathophysiological mechanisms and the lack of noninvasive, straightforward, and real-time tools, drug-induced hepatotoxicity has rarely been predicted satisfactorily. In this paper, by utilizing the reactive species peroxynitrite (ONOO(-)) as a biomarker, we present a two-photon fluorescent probe, TP-KA, holding rapid response, high specificity and sensitivity towards ONOO(-), to investigate drug (acetaminophen and tolcapone)-related liver injury and the remediate effect of N-acetyl cysteine (NAC)...
May 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28577870/mitochondria-as-the-target-for-the-modulatory-effect-of-curcumin-in-oxaliplatin-induced-toxicity-in-isolated-rat-liver-mitochondria
#19
Mohammad Waseem, Suhel Parvez, Heena Tabassum
BACKGROUND AND AIMS: To explore hepatoprotective action of curcumin (CMN, a bioflavonoid) on oxaliplatin (Oxa)-triggered mitochondrial oxidative stress and respiratory chain complexes in liver of rats. Oxa is a ubiquitously utilized platinum-based chemotherapeutic agent commonly used for the treatment of colorectal cancer. Mitochondria have recently emerged as targets for anticancer drugs in several kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. There is a dearth of evidence involving the role of mitochondria in mediating Oxa-evoked hepatotoxicity and its underlying mechanism is still debatable...
January 2017: Archives of Medical Research
https://www.readbyqxmd.com/read/28575416/toxic-drug-induced-liver-failure-during-therapy-of-rheumatoid-arthritis-with-tocilizumab-subcutaneously-a-case-report
#20
Friedrich Anger, Armin Wiegering, Johanna Wagner, Johan Lock, Johannes Baur, Lukas Haug, Marc Schmalzing, Andreas Geier, Stefan Löb, Ingo Klein
No abstract text is available yet for this article.
June 1, 2017: Rheumatology
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