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drug induced liver toxicity

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https://www.readbyqxmd.com/read/27910780/naringenin-ameliorates-doxorubicin-toxicity-and-hypoxic-condition-in-dalton-s-lymphoma-ascites-tumor-mouse-model-evidence-from-electron-paramagnetic-resonance-imaging
#1
Venkatesan Kathiresan, Swathika Subburaman, Arun Venkatesh Krishna, Mathivanan Natarajan, Gandhidasan Rathinasamy, Kumaresan Ganesan, Murugesan Ramachandran
Doxorubicin (DOX) is a well-known cytotoxic agent used extensively as a chemotherapeutic drug to eradicate a wide variety of human cancers. Reactive oxygen species (ROS)-mediated oxidative stress during DOX treatment can induce cardiac, renal, and hepatic toxicities, which can constrain its use as a potential cytotoxic agent. The present work investigates the antioxidant potential of naringenin (NAR) against DOXinduced toxicities of a Dalton's lymphoma ascites (DLA) tumor-bearing mouse model. Mice were randomized into four groups: a negative control, positive control, DOX (2...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27896850/zebrafish-larva-as-a-reliable-model-for-in-vivo-assessment-of-membrane-remodeling-involvement-in-the-hepatotoxicity-of-chemical-agents
#2
Normand Podechard, Martine Chevanne, Morgane Fernier, Arnaud Tête, Aurore Collin, Doris Cassio, Olivier Kah, Dominique Lagadic-Gossmann, Odile Sergent
The easy-to-use in vivo model, zebrafish larva, is being increasingly used to screen chemical-induced hepatotoxicity, with a good predictivity for various mechanisms of liver injury. However, nothing is known about its applicability in exploring the mechanism called membrane remodeling, depicted as changes in membrane fluidity or lipid raft properties. The aim of this study was, therefore, to substantiate the zebrafish larva as a suitable in vivo model in this context. Ethanol was chosen as a prototype toxicant because it is largely described, both in hepatocyte cultures and in rodents, as capable of inducing a membrane remodeling leading to hepatocyte death and liver injury...
November 28, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27890005/mechanism-based-inhibitors-from-phytomedicine-risks-of-hepatotoxicity-and-their-potential-hepatotoxic-substructures
#3
Lili Wang, Xin He, Chunhuan Jin, Gregory Ondieki
The adverse reactions and side effects associated with use of herbal medicines, especially their damaging effects on the liver have increasingly been reported worldwide. Some of the herbal ingredients have the potential risk of herb-induced liver injury but their hepatotoxicity mechanisms and associated risk factors are not well characterized until now. Xenobiotics are catalyzed by cytochrome P450 enzymes into highly reactive metabolites, which can covalently bind to the enzyme itself and subsequently cause mechanism-based inhibition (MBI)...
November 23, 2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27855458/-drug-induced-liver-injury
#4
Hans Christian Spangenberg
The incidence of drug induced liver injury (DILI) has been reported to be between 14 - 20 per 100 000 inhabitants. The diagnosis of DILI is based on an accurate anamnesis and exclusion of other liver diseases. Drugs most commonly involved in DILI belong to the classes of antibiotics and analgetics. The most important therapeutic issue is to identify and withdraw the toxic compound.
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27853831/role-of-the-lipid-regulated-nf-%C3%AE%C2%BAb-il-6-stat3-axis-in-alpha-naphthyl-isothiocyanate-induced-liver-injury
#5
Zhong-Ze Fang, Naoki Tanaka, Dan Lu, Chang-Tao Jiang, Wei-Hua Zhang, Chunze Zhang, Zuo Du, Zhi-Wei Fu, Peng Gao, Yun-Feng Cao, Hong-Zhi Sun, Zhi-Tu Zhu, Yan Cai, Kristopher W Krausz, Zhi Yao, Frank J Gonzalez
Alpha-naphthyl isothiocyanate (ANIT)-induced liver damage is regarded as a useful model to study drug-induced cholestatic hepatitis. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based metabolomics revealed clues to the mechanism of ANIT-induced liver injury, which facilitates the elucidation of drug-induced liver toxicity. 1-Stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:0) and 1-oleoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:1) were significantly increased in serum from ANIT-treated mice, and this increase resulted from altered expression of genes encoding the lipid metabolism enzymes Chka and Scd1...
November 16, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27848888/immunotherapy-in-liver-diseases-a-balance-between-immunity-and-tolerance
#6
Alaknanda Mishra, Pramod K Upadhyay, Perumal Nagarajan
In today's context when liver diseases have spread across countries and people of all ages, it is of high importance to consider novel methods of non-toxic and long lived therapeutics. Among various therapies, immunotherapy for acute and chronic liver diseases is rapidly moving to the forefront among treatment options in hepatology medicine. Liver has a unique immuno- biological advantage which is utilized to maintain a balance between immunity and tolerance. This intricate balance of hepatic immune cells can be modulated to effect treatments in various liver diseases...
November 16, 2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27834287/naphthoquine-induced-central-nervous-system-and-hepatic-vasculocentric-toxicity-in-the-beagle-dog
#7
Jean-Rene Galarneau, Emily K Meseck, Robert L Hall, Wenkui Li, Margaret L Weaver
Naphthoquine phosphate (NP) was considered as a partner drug with a promising antimalarial drug candidate. Here we report unexpected adverse clinical signs and microscopic findings in a canine pilot toxicology study with NP. Male and female dogs were dosed daily by oral gavage with NP at 2, 10, or 50 mg/kg/day for a maximum of 14 days. NP was not tolerated at ≥10 mg/kg/day; several animals were sacrificed in moribund condition and marked neurological clinical signs were noted at 50 mg/kg/day. The main microscopic observation was central nervous system vasculocentric inflammation (mainly lymphocytes and macrophages) in the white and gray matter of various regions of the brain at ≥2 mg/kg/day and at lower incidence in the spinal cord at ≥10 mg/kg/day...
November 9, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27832320/activation-of-nuclear-receptor-car-by-an-environmental-pollutant-perfluorooctanoic-acid
#8
Taiki Abe, Mirei Takahashi, Makoto Kano, Yuto Amaike, Chizuru Ishii, Kazuhiro Maeda, Yuki Kudoh, Toru Morishita, Takuomi Hosaka, Takamitsu Sasaki, Susumu Kodama, Atsushi Matsuzawa, Hiroyuki Kojima, Kouichi Yoshinari
Perfluorocarboxylic acids (PFCAs) including perfluorooctanoic acid (PFOA) are environmental pollutants showing high accumulation, thermochemical stability and hepatocarcinogenicity. Peroxisome proliferator-activated receptor α is suggested to mediate their toxicities, but the precise mechanism remains unclear. Previous reports also imply a possible role of constitutive androstane receptor (CAR), a key transcription factor for the xenobiotic-induced expression of various genes involved in drug metabolism and disposition as well as hepatocarcinogenesis...
November 10, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27826632/inhibition-of-pannexin1-channels-alleviates-acetaminophen-induced-hepatotoxicity
#9
Michaël Maes, Mitchell R McGill, Tereza Cristina da Silva, Chloé Abels, Margitta Lebofsky, James L Weemhoff, Taynã Tiburcio, Isabel Veloso Alves Pereira, Joost Willebrords, Sara Crespo Yanguas, Anwar Farhood, Alain Beschin, Jo A Van Ginderachter, Silvia Penuela, Hartmut Jaeschke, Bruno Cogliati, Mathieu Vinken
Pannexins constitute a relatively new family of transmembrane proteins that form channels linking the cytoplasmic compartment with the extracellular environment. The presence of pannexin1 in the liver has been documented previously, where it underlies inflammatory responses, such as those occurring upon ischemia-reperfusion injury. In the present study, we investigated whether pannexin1 plays a role in acute drug-induced liver toxicity. Hepatic expression of pannexin1 was characterized in a mouse model of acetaminophen-induced hepatotoxicity...
November 8, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27825753/in-vitro-and-in-vivo-anti-coagulant-activity-and-toxicological-studies-of-marine-sulfated-glycosaminoglycans
#10
Fatma Krichen, Zohra Ghlissi, Ikram Ben Amor, Nadhem Sayari, Rim Kallel, Jalel Gargouri, Zouheir Sahnoun, Tahia Boudawara, Ali Bougatef
The present study aimed to characterize and evaluate the in vitro and in vivo anticoagulant activity of sulfated glycosaminoglycans from the skins of smooth hound (SHSG) and grey triggerfish (GTSG). The analysis of SHSG and GTSG with acetate cellulose electrophoresis in Zn-acetate revealed the presence of hyaluronic acid (HA), chondroitin sulfate (CS) and dermatan sulfate (DS). Both glycosaminoglycans were evaluated for their in vitro anticoagulant activities using activated partial thromboplastin time (aPTT), thrombin time (TT) and prothrombine time (PT) tests...
November 5, 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/27821033/acute-temozolomide-induced-liver-injury-mixed-type-hepatocellular-and-cholestatic-toxicity
#11
C Aygun, A Y Altınok, A Çakır, A F Agan, Y Balaban
Temozolomide (TMZ) is an oral imidazotetrazine methylating agent which is used for the treatment of glioblastoma multiforme (GBM). We report a case of acute hepatotoxicity in a 53-year old male patient after administration of TMZ for GBM. He had fatigue, nausea, anorexia and jaundice. His laboratory analysis showed alanine aminotransferase(ALT): 632 IU/L (normal range 0-40); aspartate aminotransferase(AST): 554 IU/L (normal range 5-34); alkaline phosphatase(ALP): 1143 IU/L (normal range 40-150); γ-glutamyl transpeptidase(GGT): 514 IU/L (normal range 9-64 IU/L); total bilirubin: 15...
July 2016: Acta Gastro-enterologica Belgica
https://www.readbyqxmd.com/read/27818731/prediction-of-non-genotoxic-carcinogenicity-based-on-genetic-profiles-of-short-term-exposure-assays
#12
Luis Orlando Pérez, Rolando González-José, Pilar Peral García
Non-genotoxic carcinogens are substances that induce tumorigenesis by non-mutagenic mechanisms and long term rodent bioassays are required to identify them. Recent studies have shown that transcription profiling can be applied to develop early identifiers for long term phenotypes. In this study, we used rat liver expression profiles from the NTP (National Toxicology Program, Research Triangle Park, USA) DrugMatrix Database to construct a gene classifier that can distinguish between non-genotoxic carcinogens and other chemicals...
October 2016: Toxicological Research
https://www.readbyqxmd.com/read/27816492/tremelimumab-in-combination-with-ablation-in-patients-with-advanced-hepatocellular-carcinoma
#13
Austin G Duffy, Susanna V Ulahannan, Oxana Makorova-Rusher, Osama Rahma, Heiner Wedemeyer, Drew Pratt, Jeremy L Davis, Marybeth S Hughes, Theo Heller, Mei ElGindi, Ashish Uppala, Firouzeh Korangy, David E Kleiner, William D Figg, David Venzon, Seth M Steinberg, Aradhana M Venkatesan, Venkatesh Krishnasamy, Nadine Abi-Jaoudeh, Elliot Levy, Brad J Wood, Tim F Greten
BACKGROUND: Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 on the surface of activated T lymphocytes. Ablative therapies have been shown to induce a peripheral immune response which may enhance the effect of anti-CTLA4 treatment in patients with advanced HCC. METHODS: Patients with HCC [Childs Pugh A/B7; Barcelona Clinic Liver Cancer Stage B/C; ECOG 0/1] were enrolled in a study of tremelimumab in combination with an ablative procedure performed during week 6...
November 2, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27814544/chemical-and-toxicological-characterisation-of-anticancer-drugs-in-hospital-and-municipal-wastewaters-from-slovenia-and-spain
#14
Marina Isidori, Margherita Lavorgna, Chiara Russo, Michael Kundi, Bojana Žegura, Matjaž Novak, Metka Filipič, Miroslav Mišík, Siegfried Knasmueller, Miren López de Alda, Damià Barceló, Božo Žonja, Marjeta Česen, Janez Ščančar, Tina Kosjek, Ester Heath
Anticancer drugs are continuously released into hospital and urban wastewaters, where they, most commonly, undergo conventional treatment in wastewater treatment plants (WWTPs). Wastewaters contain complex mixtures of substances including parent compounds, their metabolites and transformation products (TPs). In this study, samples of hospital effluents and WWTP influents and effluents from Slovenia and Spain were analyzed for twenty-two selected anticancer drugs, their metabolites and transformation products...
October 28, 2016: Environmental Pollution
https://www.readbyqxmd.com/read/27810556/transporter-occluded-state-conformation-induced-endocytosis-amino-acid-transporter-atb-0-mediated-tumor-targeting-of-liposomes-for-docetaxel-delivery-for-hepatocarcinoma-therapy
#15
Qiuhua Luo, Ping Gong, Mengchi Sun, Longfa Kou, Vadivel Ganapathy, Yongkui Jing, Zhonggui He, Jin Sun
Rapidly proliferating tumor cells upregulate specific amino acid transporters, which hold great potential for tumor-selective drug delivery. Published reports have focused primarily on blocking these transporters as a means of starving the tumor cells of amino acids, but their potential in drug delivery remains understudied. In the present study, we developed liposomes functionalized with lysine and polyoxyethylene stearate conjugate (LPS) to interact with ATB(0,+), an amino acid transporter overexpressed in hepatocarcinoma and the liver cancer cell line HepG2...
November 1, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27808117/evaluation-of-uttroside-b-a-saponin-from-solanum-nigrum-linn-as-a-promising-chemotherapeutic-agent-against-hepatocellular-carcinoma
#16
Lekshmi R Nath, Jaggaiah N Gorantla, Arun Kumar T Thulasidasan, Vinod Vijayakurup, Shabna Shah, Shabna Anwer, Sophia M Joseph, Jayesh Antony, Kollery Suresh Veena, Sankar Sundaram, Udaya K Marelli, Ravi S Lankalapalli, Ruby John Anto
We report, for the first time, the remarkable efficacy of uttroside B, a potent saponin from Solanum nigrum Linn, against liver cancer. The compound has been isolated and characterized from the leaves of Solanum nigrum Linn, a plant widely used in traditional medicine and is a rich resource of several anticancer molecules. Uttroside B, that comprises of β-D-glucopyranosyl unit at C-26 of the furostanol and β-lycotetraosyl unit at C-3, is ten times more cytotoxic to the liver cancer cell line, HepG2 (IC50: 0...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27805256/homocysteine-alcoholism-and-its-potential-epigenetic-mechanism
#17
REVIEW
Pradip K Kamat, Carissa J Mallonee, Akash K George, Suresh C Tyagi, Neetu Tyagi
Alcohol is the most socially accepted addictive drug. Alcohol consumption is associated with some health problems such as neurological, cognitive, behavioral deficits, cancer, heart, and liver disease. Mechanisms of alcohol-induced toxicity are presently not yet clear. One of the mechanisms underlying alcohol toxicity has to do with its interaction with amino acid homocysteine (Hcy), which has been linked with brain neurotoxicity. Elevated Hcy impairs with various physiological mechanisms in the body, especially metabolic pathways...
December 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/27802299/protective-effects-of-essential-oils-as-natural-antioxidants-against-hepatotoxicity-induced-by-cyclophosphamide-in-mice
#18
Salah A Sheweita, Lobna S El-Hosseiny, Munther A Nashashibi
Clinical application of cyclophosphamide (CP) as an anticancer drug is often limited due to its toxicity. CP is metabolized mainly in the liver by cytochrome P450 system into acrolein which is the proximate toxic metabolite. Many different natural antioxidants were found to alleviate the toxic effects of various toxic agents via different mechanisms. Therefore, the present study aimed at investigating the role of essential oils extracted from fennel, cumin and clove as natural antioxidants in the alleviation of hepatotoxicity induced by CP through assessment of hepatotoxicity biomarkers (AST, ALT, ALP), histopathology of liver tissues as well as other biochemical parameters involved in the metabolism of CP...
2016: PloS One
https://www.readbyqxmd.com/read/27793116/the-incidence-presentation-outcomes-risk-of-mortality-and-economic-data-of-drug-induced-liver-injury-from-a-national-database-in-thailand-a-population-base-study
#19
Abhasnee Sobhonslidsuk, Kittiyod Poovorawan, Ngamphol Soonthornworasiri, Wirichada Pan-Ngum, Kamthorn Phaosawasdi
BACKGROUND: Toxic liver diseases are mainly caused by drug-induced liver injury (DILI). We assessed incidences and outcomes of DILI including associated factors for mortality. METHODS: We performed a population-based study of hospitalized patients with DILI. Information was retrieved from the Nationwide Hospital Admission Data using ICD-10 code of toxic liver diseases (K71) and additional codes (T36-T65). The associated factors were analyzed with log-rank test, univariate and multiple cox regression analysis...
October 28, 2016: BMC Gastroenterology
https://www.readbyqxmd.com/read/27793006/hs-173-a-novel-pi3k-inhibitor-suppresses-emt-and-metastasis-in-pancreatic-cancer
#20
Marufa Rumman, Kyung Hee Jung, Zhenghuan Fang, Hong Hua Yan, Mi Kwon Son, Soo Jung Kim, Juyoung Kim, Jung Hee Park, Joo Han Lim, Sungwoo Hong, Soon-Sun Hong
Pancreatic cancer is one of the most aggressive solid malignancies prone to metastasis. Epithelial-mesenchymal transition (EMT) contributes to cancer invasiveness and drug resistance. In this study, we investigated whether HS-173, a novel PI3K inhibitor blocked the process of EMT in pancreatic cancer. HS-173 inhibited the growth of pancreatic cancer cells in a dose- and time-dependent manner. Moreover, it significantly suppressed the TGF-β-induced migration and invasion, as well as reversed TGF-β-induced mesenchymal cell morphology...
October 25, 2016: Oncotarget
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