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drug induced liver toxicity

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https://www.readbyqxmd.com/read/28805879/downregulation-of-hepatic-multi-drug-resistance-protein-1-mdr1-after-copper-exposure
#1
Sara Reinartz Groba, Sarah Guttmann, Christoph Niemietz, Friedrich Bernick, Vanessa Sauer, Oliver Hachmöller, Uwe Karst, Hans Zischka, Andree Zibert, Hartmut H Schmidt
Copper homeostasis is strictly regulated in mammalian cells. We investigated the adaptation of hepatocytes after long-term copper exposure. Copper-resistant hepatoma HepG2 cell lines lacking ATP7B were generated. Growth, copper accumulation, gene expression, and transport were determined. Hepatocyte-like cells derived from a Wilson disease (WD) patient and the liver of a WD animal model were also studied. The rapidly gained copper resistance was found to be stable, as subculturing of cells in the absence of added copper (weaning) did not restore copper sensitivity...
August 14, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28803824/the-clinical-spectrum-of-hepatic-manifestations-in-chronic-lymphocytic-leukemia
#2
REVIEW
Natalia Kreiniz, Ofrat Beyar Katz, Aaron Polliack, Tamar Tadmor
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world, characterized by the presence of long-lived circulating leukemic cells in the peripheral blood that may infiltrate all organs, particularly those of the reticulo-endothelial system. Liver enlargement and elevation of liver enzymes related to specific involvement by the underlying disease are well-recognized features in these patients. In CLL, the differential diagnosis of liver disorders is broad and includes liver infiltration by leukemic cells, immunologic manifestations associated with CLL, primary and secondary hepatic malignancies, drug-induced hepatotoxicity, infections, and Richter transformation...
July 23, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28800917/thyrotoxic-rubber-antioxidants-2-mercaptobenzimidazole-and-its-methyl-derivatives-cause-both-inhibition-and-induction-of-drug-metabolizing-activity-in-rat-liver-microsomes-after-repeated-oral-administration
#3
Atsuko Miyajima, Kazue Sakemi-Hoshikawa, Makoto Usami, Katsuyoshi Mitsunaga, Tomohiko Irie, Yasuo Ohno, Momoko Sunouchi
We examined the effects of thyrotoxic rubber antioxidants, 2-mercaptobenzimidazole (MBI, 0.3 mmol/kg/day) and its methyl derivatives, methyl-MBIs [4-methyl-MBI (4-MeMBI, 0.6 mmol/kg/day), 5-methyl-MBI (5-MeMBI, 0.6 mmol/kg/day), and 4(or 5)-methyl-MBI (4(5)-MeMBI, 0.6 or 1.2 mmol/kg/day)], on the drug-metabolizing activity in male rat liver microsomes by 8-day repeated oral administration. The weight of liver and thyroid were increased by all the test chemicals; MBI was most potent, and there was no additive or synergistic effect between 4-MeMBI and 5-MeMBI...
August 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28798938/evidence-for-tissue-toxicity-in-balb-c-exposed-to-a-long-term-treatment-with-oxiranes-compared-to-meglumine-antimoniate
#4
Luiz Filipe Gonçalves Oliveira, Franklin Souza-Silva, Léa Cysne-Finkelstein, Kíssila Rabelo, Juliana Fernandes Amorim, Adriana de Souza Azevedo, Saulo Cabral Bourguignon, Vitor Francisco Ferreira, Marciano Viana Paes, Carlos Roberto Alves
Leishmaniasis remains a serious public health problem in developing countries without effective control, whether by vaccination or chemotherapy. Part of the failure of leishmaniasis control is due to the lack of new less toxic and more effective drugs able to eliminate both the lesions and the parasite. Oxiranes derived from naphthoquinones now being assayed are promising drugs for the treatment of this group of diseases. The predicted pharmacokinetic properties and toxicological profiles of epoxy-α-lapachone and epoxymethoxy-lawsone have now been compared to those of meglumine antimoniate, and histological changes induced by these drugs in noninfected BALB/c mice tissues are described...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28797532/assessment-of-in-vitro-antifungal-efficacy-and-in-vivo-toxicity-of-amphotericin-b-loaded-plga-and-plga-peg-blend-nanoparticles
#5
T C Moraes Moreira Carraro, C Altmeyer, N Maissar Khalil, R Mara Mainardes
Amphotericin B (AmB) is widely applied in treatment of systemic fungal infections. However, the emergence of severe adverse effects, such as nephrotoxicity, hepatotoxicity and hemolytic anemia, can limit its clinical use. Poly(lactide-co-glycolide) (PLGA) or poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) blend nanoparticles containing AmB were developed with the aim to decrease AmB toxicity and propose the oral route for AmB delivery. Nanoparticles were characterized by particle size, polydispersity index, Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction analyses...
August 7, 2017: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/28772086/highlights-of-drug-and-herb-induced-liver-injury-in-the-literature-from-2016-how-best-to-translate-new-information-into-clinical-practice
#6
Omar Shahbaz, Sandeep Mahajan, James H Lewis
INTRODUCTION: More than 1500 papers on drug-induced liver injury (DILI) and herb-induced liver injury (HILI) were published in 2016, many of which have the potential to impact clinical practice. AREAS COVERED: Clinical studies and case series that lent themselves to new concepts or directions in diagnosing, preventing, and treating DILI were selected for inclusion. Epidemiology of DILI in large prospective registries was highlighted, including the US DILIN network and Spanish DILI registry...
August 3, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28766385/paracetamol-overdose-induced-oxidative-stress-toxicity-metabolism-and-protective-effects-of-various-compounds-in-vivo-and-in-vitro
#7
Xu Wang, Qinghua Wu, Aimei Liu, Arturo Anadón, José-Luis Rodríguez, María-Rosa Martínez-Larrañaga, Zonghui Yuan, María-Aránzazu Martínez
Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress...
August 16, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28766171/cisplatin-and-cisplatin-analogues-perfusion-through-isolated-rat-heart-the-effects-of-acute-application-on-oxidative-stress-biomarkers
#8
Isidora M Stojic, Vladimir I Zivkovic, Ivan M Srejovic, Tamara R Nikolic, Nevena S Jeremic, Jovana N Jeremic, Dragan M Djuric, Nemanja Jovicic, Katarina G Radonjic, Zivadin D Bugarcic, Vladimir L J Jakovljevic, Slobodan S Novokmet
Drug-induced oxidative stress can occur in numerous tissues and organ systems (liver, kidney, ear, nervous system, and cardiovascular system). Cancer therapy with cisplatin is associated with side effects to which oxidative stress may contribute. We have compared the influences of cisplatin (reference compound) and its' analogues (dichloro(1,2-diaminocyclohexane)platinum(II) and chloro(2,2':6',2″-terpyridine)platinum(II)) in a model of isolated rat heart using the Langendorff technique. The production of oxidative stress biomarkers, antioxidant enzymes, myocardial damage, and expression of Bax, OH-1, and SODs were studied...
August 1, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28762043/customised-in-vitro-model-to-detect-human-metabolism-dependent-idiosyncratic-drug-induced-liver-injury
#9
Laia Tolosa, Nuria Jiménez, Gabriela Pérez, José V Castell, M José Gómez-Lechón, M Teresa Donato
Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify metabolic phenotypes with increased susceptibility to DILI...
July 31, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28754304/a-natural-ccr2-antagonist-relieves-tumor-associated-macrophage-mediated-immunosuppression-to-produce-a-therapeutic-effect-for-liver-cancer
#10
Wenbo Yao, Qian Ba, Xiaoguang Li, Huiliang Li, Shoude Zhang, Ya Yuan, Feng Wang, Xiaohua Duan, Jingquan Li, Weidong Zhang, Hui Wang
Hepatocellular carcinoma (HCC) is a common malignant tumor in the digestive tract with limited therapeutic choices. Although sorafenib, an orally administered multikinase inhibitor, has produced survival benefits for patients with advanced HCC, favorable clinical outcomes are limited due to individual differences and resistance. The application of immunotherapy, a promising approach for HCC is urgently needed. Macrophage infiltration, mediated by the CCL2/CCR2 axis, is a potential immunotherapeutic target. Here, we report that a natural product from Abies georgei, named 747 and related in structure to kaempferol, exhibits sensitivity and selectivity as a CCR2 antagonist...
August 2017: EBioMedicine
https://www.readbyqxmd.com/read/28748471/evaluation-of-mitochondrial-respiration-in-cultured-rat-hepatocytes
#11
Jean-Pierre Marchandeau, Gilles Labbe
Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver injury and other serious side effects, such as lactic acidosis and rhabdomyolysis, in some patients. Several in vitro and in vivo investigations can be performed in order to determine if drugs can disturb mitochondrial fatty acid oxidation (FAO) and the oxidative phosphorylation (OXPHOS) process, deplete hepatic mitochondrial DNA (mtDNA), or trigger the opening of the mitochondrial permeability transition pore (MPT). Among these investigations, mitochondrial respiration is a relatively easy test to measure the potential toxicity of a drug...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28748198/abacavir-dolutegravir-lamivudine-triumeq-induced-liver-toxicity-in-a-human-immunodeficiency-virus-infected-patient
#12
Erin S Christensen, Rupali Jain, Alison C Roxby
Drug-induced liver injury related to Triumeq (abacavir/lamivudine/dolutegravir) has not been reported in clinical trials. We report a case of hepatotoxicity related to Triumeq exposure in a human immunodeficiency virus-infected patient. Clinicians should remain aware of the risk for acute and late-onset hepatitis with these agents. Close monitoring is recommended.
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28747986/comparison-of-therapeutic-responses-to-an-anticancer-drug-in-three-stocks-of-icr-mice-derived-from-three-different-sources
#13
Ji Eun Sung, Ji Eun Kim, Hyun Ah Lee, Woo Bin Yun, Jun Young Choi, Mi Rim Lee, Jin Ju Park, Hye Ryeong Kim, Bo Ram Song, Young Suk Jung, Kil Soo Kim, Dae Youn Hwang
Korl:ICR mice, established by the Korean National Institute of Food and Drug Safety Evaluation (NIFDS), are characterized based on their genetic variation, response to gastric injury, and response to constipation inducers. To compare the inhibitory responses of ICR stocks obtained from three different sources to the anticancer drug cisplatin (Cis), alterations in tumor volume, histopathological structure, and toxicity were examined in Sarcoma 180 tumor-bearing Korl:ICR, A:ICR (USA source), and B:ICR (Japan source) mice treated with low and high concentrations of Cis (L-Cis and H-Cis, respectively)...
June 2017: Laboratory Animal Research
https://www.readbyqxmd.com/read/28743553/systematic-evaluation-of-the-toxicity-and-biodistribution-of-virus-mimicking-mucus-penetrating-dlpc-nps-as-oral-drug-delivery-system
#14
Wei Shan, Yi Cui, Min Liu, Lei Wu, Yucheng Xiang, Quan Guo, Zhirong Zhang, Yuan Huang
Development of nanoparticle (NP) to simultaneously overcome the diffusion and absorption barrier has drawn much attention. Our group recently demonstrated that the virus mimicking dilauroylphosphatidylcholine functionalized NP (DLPC-NP) could rapidly penetrate across mucus layer and subsequently enter epithelia effectively, and exhibited high potential for oral drug delivery. However, the safety of the NP has provoked some scientific concerns, which debates from their properties that circuiting the protections of mucus and exhibiting strong interaction with cell membrane...
July 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28740200/physiologically-based-modelling-in-mice-suggests-an-aggravated-loss-of-clearance-capacity-after-toxic-liver-damage
#15
Arne Schenk, Ahmed Ghallab, Ute Hofmann, Reham Hassan, Michael Schwarz, Andreas Schuppert, Lars Ole Schwen, Albert Braeuning, Donato Teutonico, Jan G Hengstler, Lars Kuepfer
Diseases and toxins may lead to death of active liver tissue, resulting in a loss of total clearance capacity at the whole-body level. However, it remains difficult to study, whether the loss of metabolizing tissue is sufficient to explain loss of metabolic capacity of the liver or whether the surviving tissue undergoes an adaptive response to compensate the loss. To understand the cellular impact of toxic liver damage in an in vivo situation, we here used physiologically-based pharmacokinetic modelling to investigate pharmacokinetics of a specifically designed drug cocktail at three different sampling sites of the body in healthy mice and mice treated with carbon tetrachloride (CCl4)...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28737131/pharmacokinetics-of-flucloxacillin-and-its-metabolites-in-patients-with-renal-failure-impact-on-liver-toxicity%C3%A2
#16
Alexandra Maier-Salamon, Salwa Ahmed Elgendy, Brigitte Meyer, Matthias Vossen, Theresia Thalhammer, Florian Thalhammer, Walter Jäger
OBJECTIVE: The antimicrobial agent flucloxacillin is a potential cause of drug-induced liver disease, but the underlying mechanisms for toxicity have not been fully elucidated. As in-vitro and in-vivo findings suggest that biotransformation products contribute to hepatotoxicity, the purpose of this study was to characterize formation and accumulation of its metabolites in patients with renal failure. METHODS: Twelve intensive care patients undergoing continuous venovenous hemofiltration received 4...
July 24, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28729056/discovery-and-structure-activity-relationship-of-auriculatone-a-potent-hepatoprotective-agent-against-acetaminophen-induced-liver-injury
#17
Meng Zhou, Min Wang, Rui-Feng Zhong, Xiang-Ming Liao, Lian-Li Deng, Guo-Bo Xu, Xun He, Jing Li, Yong-Jun Li, Ting Liu, Yong-Lin Wang, Shang-Gao Liao
Acetaminophen (APAP, paracetamol) overdose has been the most frequent cause of drug-induced liver failure. APAP-induced liver toxicity can be fatal in many cases even with treatment of the clinically used N-acetylcysteine (NAC), and the need for novel therapeutic agents is apparent. Through evaluating the hepatoprotective effects of the co-occurring substances present in oleanolic acid tablets which have been used in China for decades as an adjuvant therapy for acute and chronic hepatitis, auriculatone was found to protect HL-7702 cells from APAP-induced liver injury comparable to NAC at the concentration of 10μM...
July 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28726775/oroxylin-a-activates-pkm1-hnf4-alpha-to-induce-hepatoma-differentiation-and-block-cancer-progression
#18
Libin Wei, Yuanyuan Dai, Yuxin Zhou, Zihao He, Jingyue Yao, Li Zhao, Qinglong Guo, Lin Yang
Liver cancer is the second cause of death from cancer worldwide, without effective treatment. Traditional chemotherapy for liver cancer has big side effects for patients, whereas targeted drugs, such as sorafenib, commonly have drug resistance. Oroxylin A (OA) is the main bioactive flavonoids of Scutellariae radix, which has strong anti-hepatoma effect but low toxicity to normal tissue. To date, no differentiation-inducing agents have been reported to exert a curative effect on solid tumors. Here our results demonstrated that OA restrained the proliferation and induced differentiation of hepatoma both in vitro and in vivo, via inducing a high PKM1 (pyruvate kinase M1)/PKM2 (pyruvate kinase M2) ratio...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28722244/risk-of-liver-decompensation-with-cumulative-use-of-mitochondrial-toxic-nucleoside-analogues-in-hiv-hepatitis-c-virus-coinfection
#19
Vincent Lo Re Rd, Bret Zeldow, Michael J Kallan, Janet P Tate, Dena M Carbonari, Sean Hennessy, Jay R Kostman, Joseph K Lim, Matthew Bidwell Goetz, Robert Gross, Amy C Justice, Jason A Roy
PURPOSE: Among patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death. METHODS: We conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients...
July 19, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28717830/a-review-of-drug-induced-liver-injury-databases
#20
REVIEW
Guangwen Luo, Yiting Shen, Lizhu Yang, Aiping Lu, Zheng Xiang
Drug-induced liver injuries have been a major focus of current research in drug development, and are also one of the major reasons for the failure and withdrawal of drugs in development. Drug-induced liver injuries have been systematically recorded in many public databases, which have become valuable resources in this field. In this study, we provide an overview of these databases, including the liver injury-specific databases LiverTox, LTKB, Open TG-GATEs, LTMap and Hepatox, and the general databases, T3DB, DrugBank, DITOP, DART, CTD and HSDB...
July 17, 2017: Archives of Toxicology
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