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drug induced liver toxicity

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https://www.readbyqxmd.com/read/28729056/discovery-and-structure-activity-relationship-of-auriculatone-a-potent-hepatoprotective-agent-against-acetaminophen-induced-liver-injury
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28717109/utility-of-human-hepatocyte-spheroids-without-feeder-cells-for-evaluation-of-hepatotoxicity
#5
Takuo Ogihara, Hiroshi Arakawa, Tomoko Jomura, Yoko Idota, Satoshi Koyama, Kentaro Yano, Hajime Kojima
We investigated the utility of three-dimensionally cultured hepatocytes (spheroids) without feeder cells (Sph(f-)) for the prediction of drug-induced liver injury (DILI) in humans. Sph(f-) and spheroids cultured on feeder cells (Sph(f+)) were exposed to the hepatotoxic drugs flutamide, diclofenac, isoniazid and chlorpromazine at various concentrations for 14 days, and albumin secretion and cumulative leakages of toxicity marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GTP), were measured...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28713494/caspase-3-role-and-immunohistochemical-expression-in-assessment-of-apoptosis-as-a-feature-of-h1n1-vaccine-caused-drug-induced-liver-injury-dili
#6
Abir Khalil Mohamed, Mona Magdy
BACKGROUND: Drug-Induced Liver Injury (DILI) changes, occur post exposure to natural or chemical compounds including apoptosis. AIM: To assess the H1N1 vaccine-caused DILI by histochemical and immunohistochemical methods. METHODS: This 2014's experimental study was conducted on 70 albino rats. They were given Arepanrix(TM) H1N1 vaccine and were divided into 7 groups; 10 mice each, as control (non-vaccinated), vac2 and vac4 injected with 1(st) and 2(nd) doses of vaccine (suspension only) and euthanized after 3 weeks each, vac5 euthanized 6 weeks after 2(nd) dose, mix2 and mix4 injected with 1(st) and 2(nd) doses of vaccine (mixture of suspension and adjuvant) and euthanized after 3 weeks each, mix5 and euthanized 6 weeks after 2(nd) dose...
May 2017: Electronic Physician
https://www.readbyqxmd.com/read/28709620/synthesis-and-anti-diabetic-activity-of-new-n-n-dimethylphenylenediamine-derivatized-nitrilotriacetic-acid-vanadyl-complexes
#7
Xia Niu, Jichun Yang, Xiaoda Yang
Vanadium compounds are promising anti-diabetic agents. However, reducing the metal toxicity while keeping/improving the hypoglycemic effect is still a big challenge towards the success of anti-diabetic vanadium drugs. To improve the therapeutic potency using the anti-oxidative strategy, we synthesized new N,N-dimethylphenylenediamine (DMPD)-derivatized nitrilotriacetic acid vanadyl complexes ([VO(dmada)]). The in vitro biological evaluations revealed that the DMPD-derivatized complexes showed improved antioxidant capacity and lowered cytotoxicity on HK-2 cells than bis(maltolato)oxidovanadium (IV) (BMOV)...
July 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28699415/a-scalable-approach-for-the-generation-of-human-pluripotent-stem-cell-derived-hepatic-organoids-with-sensitive-hepatotoxicity-features
#8
Malte Sgodda, Zhen Dai, Robert Zweigerdt, Amar D Sharma, Michael Ott, Tobias Cantz
The quest for physiologically-active human hepatocyte-like cells for in vitro research and drug screening is high. The recent progress in the field of pluripotent stem cell (PSC) - derived hepatic cells within the last decade brings those cells closer to applications in translational medicine. However, the classical two-dimensional (2D) cell culture systems are of limited use, because relevant cell-cell interactions based on cell polarity, which is a major prerequisite for proper hepatic cell metabolisms, are not provided...
July 12, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28695300/new-fty720-docetaxel-nanoparticle-therapy-overcomes-fty720-induced-lymphopenia-and-inhibits-metastatic-breast-tumour-growth
#9
Heba Alshaker, Qi Wang, Shyam Srivats, Yimin Chao, Colin Cooper, Dmitri Pchejetski
PURPOSE: Combining molecular therapies with chemotherapy may offer an improved clinical outcome for chemoresistant tumours. Sphingosine-1-phosphate (S1P) receptor antagonist and sphingosine kinase 1 (SK1) inhibitor FTY720 (FTY) has promising anticancer properties, however, it causes systemic lymphopenia which impairs its use in cancer patients. In this study, we developed a nanoparticle (NP) combining docetaxel (DTX) and FTY for enhanced anticancer effect, targeted tumour delivery and reduced systemic toxicity...
July 10, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28694744/protective-effects-of-chrysin-against-drugs-and-toxic-agents
#10
REVIEW
Saeed Samarghandian, Tahereh Farkhondeh, Mohsen Azimi-Nezhad
ISSUES: Polyphenolic compounds, especially flavonoids, are known as the most common chemical class of phytochemicals, which possess a multiple range of health-promoting effects. Flavonoids are ubiquitous in nature. They are also present in food, providing an essential link between diet and prevention of several diseases. APPROACH: Chrysin (CH), a natural flavonoid, was commonly found in propolis and honey and traditionally used in herbal medicine. A growing body of scientific evidence has shown that CH possesses protective effects against toxic agents in various animal tissues, including brain, heart, liver, kidney, and lung...
April 2017: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/28689766/acute-administration-of-tramadol-and-tapentadol-at-effective-analgesic-and-maximum-tolerated-doses-causes-hepato-and-nephrotoxic-effects-in-wistar-rats
#11
Joana Barbosa, Juliana Faria, Sandra Leal, Luís Pedro Afonso, João Lobo, Odília Queirós, Roxana Moreira, Félix Carvalho, Ricardo Jorge Dinis-Oliveira
Tramadol and tapentadol are two atypical synthetic opioid analgesics, with monoamine reuptake inhibition properties. Mainly aimed at the treatment of moderate to severe pain, these drugs are extensively prescribed for multiple clinical applications. Along with the increase in their use, there has been an increment in their abuse, and consequently in the reported number of adverse reactions and intoxications. However, little is known about their mechanisms of toxicity. In this study, we have analyzed the in vivo toxicological effects in liver and kidney resulting from an acute exposure of a rodent animal model to both opioids...
July 6, 2017: Toxicology
https://www.readbyqxmd.com/read/28688987/tumor-targeting-by-lentiviral-vectors-combined-with-magnetic-nanoparticlesin-mice
#12
Ester Borroni, Marta Miola, Sara Ferraris, Giulia Ricci, Kristina ŽužekRožman, Nina Kostevšek, Angela Catizone, Lia Rimondini, Maria Prat, Enrica Verné, Antonia Follenzi
Nanomaterials conjugated or complexed with biological moieties such as antibodies, polymers or peptides appear to be suitable not only for drug delivery but also for specific cancer treatment. Here, biocompatible iron oxide magnetic nanoparticles (MNPs) with or without a silica shell coupled with lentiviral vectors (LVs) are proposed as a combined therapeutic approach to specifically target gene expression in a cancer mouse model. Initially, four different MNPs were synthesized and their physical properties were characterized to establish and discriminate their behaviors...
July 5, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28687704/synergistic-cytotoxicity-from-drugs-and-cytokines-in-vitro-as-an-approach-to-classify-drugs-according-to-their-potential-to-cause-idiosyncratic-hepatotoxicity-a-proof-of-concept-study
#13
Ashley R Maiuri, Bronlyn Wassink, Jonathan D Turkus, Anna B Breier, Theresa Lansdell, Gurpreet Kaur, Sarah L Hession, Patricia E Ganey, Robert A Roth
Idiosyncratic, drug-induced liver injury (IDILI) typically occurs in a small fraction of patients and has resulted in removal of otherwise efficacious drugs from the market. Current preclinical testing methods are ineffective in predicting which drug candidates have IDILI liability. Recent results suggest that immune mediators such as tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN) interact with drugs that cause IDILI to kill hepatocytes. This proof-of-concept study was designed to test the hypothesis that drugs can be classified according to their ability to cause IDILI in humans using logistic regression modeling with covariates derived from concentration-response relationships that describe cytotoxic interaction with cytokines...
July 7, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28685347/potential-for-a-novel-manganese-porphyrin-compound-as-adjuvant-canine-lymphoma-therapy
#14
M K Boss, M W Dewhirst, R S Sampaio, A Bennett, A Tovmasyan, K G Berman, A W Beaven, D A Rizzieri, I Batinic-Haberle, M L Hauck, I Spasojevic
PURPOSE: Manganese porphyrins are redox-active drugs and superoxide dismutase mimics, which have been shown to chemosensitize lymphoma, a cancer which frequently occurs in dogs. This study aimed to identify critical information regarding the pharmacokinetics and toxicity of Mn(III) meso-tetrakis (N-n-butoxyetylpyridium-2-yl) porphyrin, (MnTnBuOE-2-PyP(5+), MnBuOE) in dogs as a prelude to a clinical trial in canine lymphoma patients. METHODS: A single-dose pharmacokinetic (PK) study in normal dogs was performed to determine the plasma half-life (t 1/2) of MnBuOE...
July 6, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28680622/a-case-of-reversible-drug-induced-liver-failure
#15
Mohammad Ansari, Sabrina Arshed, Mohammed Islam, Shuvendu Sen, Abdalla Yousif
Acute fulminant liver failure and acute renal failure are devastating complications caused by many drugs. The use of N-acetylcysteine has been well established in acetaminophen toxicity, but it remains controversial in other cases. Dialysis is a very effective method of removing certain drugs from the system. With the invention of new street drugs such as "synthetic marijuana," it may be beneficial in patients whom the substances ingested are unknown. We report a case of a 42-year-old male who developed acute fulminant hepatic failure and acute renal failure, who was cured with dialysis, N-acetylcysteine, and other supportive measures...
July 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28678845/polymerase-free-measurement-of-microrna-122-with-single-base-specificity-using-single-molecule-arrays-detection-of-drug-induced-liver-injury
#16
David M Rissin, Barbara López-Longarela, Salvatore Pernagallo, Hugh Ilyine, A D Bastiaan Vliegenthart, James W Dear, Juan J Díaz-Mochón, David C Duffy
We have developed a single probe method for detecting microRNA from human serum using single molecule arrays, with sequence specificity down to a single base, and without the use of amplification by polymerases. An abasic peptide nucleic acid (PNA) probe-containing a reactive amine instead of a nucleotide at a specific position in the sequence-for detecting a microRNA was conjugated to superparamagnetic beads. These beads were incubated with a sample containing microRNA, a biotinylated reactive nucleobase-containing an aldehyde group-that was complementary to the missing base in the probe sequence, and a reducing agent...
2017: PloS One
https://www.readbyqxmd.com/read/28675360/four-years-of-hepatic-transplantation-in-the-republic-of-moldova
#17
Vladimir Hotineanu, Adrian Hotineanu, Serghei Burgoci, Grigore Ivancov, Natalia Taran, Angela Peltec, Dumitru Cazacu, Vitalie Sîrghi
Ever since the first liver transplant in the Republic of Moldova in 2013 we have performed 30 liver transplantations, the first having been performed in collaboration with the surgical team from Romania, led by Professor Irinel Popescu. The serious deficit of available cadaveric organs has forced us to begin with right hemi-liver transplantation from a living donor. In one third of liver transplantations we used right hemi-liver graft from a living donor, and in 2/3 of cases whole liver graft was harvested from brain-dead donors...
May 2017: Chirurgia
https://www.readbyqxmd.com/read/28675031/efficient-two-photon-fluorescent-probe-for-glutathione-s-transferase-detection-and-imaging-in-drug-induced-liver-injury-sample
#18
Jing Zhang, Zhen Jin, Xiao-Xiao Hu, Hong-Min Meng, Jin Li, Xiao-Bing Zhang, Hong-Wen Liu, Tanggang Deng, Shan Yao, Lili Feng
Drug-induced liver injury (DILI) is a potential complication of any prescribed medication. So far, the diagnosis of DILI is still a clinical challenge due to the lack of efficient diagnosis method. Glutathione S-transferase (GST), with a high concentration in liver cytosol, can reduce toxicity and facilitate urinary excretion by catalyzing the conjugation of glutathione (GSH) with reactive metabolites in liver. When liver is seriously damaged, GST and GSH will be released into plasma from liver cytosol, which caused a lower GST activity in liver cytosol...
July 4, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28673699/plasma-metabolomics-study-of-the-hepatoprotective-effect-of-glycyrrhetinic-acid-on-realgar-induced-sub-chronic-hepatotoxicity-in-mice-via-1-h-nmr-analysis
#19
Taoguang Huo, Ying Fang, Yinghua Zhang, Yanlei Wang, Cong Feng, Mingmei Yuan, Shouyun Wang, Mo Chen, Hong Jiang
ETHNOPHARMACOLOGICAL RELEVANCE: Realgar, a type of mineral drug that contains arsenic, is concurrently used with Glycyrrhizae Radx et Rhizoma to reduce its toxicity in many Chinese herbal formulations. Glycyrrhetinic acid (GA) is the bioactive ingredient in Glycyrrhizae Radx et Rhizoma. In this study, the protective effects of GA on realgar-induced hepatotoxicity was investigated using (1)H nuclear magnetic resonance ((1)H NMR)-based metabolomic approaches. MATERIALS AND METHODS: Mice were divided into control, GA, realgar, and GA and realgar co-administration groups...
July 1, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28669771/antidiabetic-antioxidant-and-anti-inflammatory-properties-of-water-and-n-butanol-soluble-extracts-from-saharian-anvillea-radiata-in-high-fat-diet-fed-mice
#20
Chouaib Kandouli, Mathieu Cassien, Anne Mercier, Caroline Delehedde, Emilie Ricquebourg, Pierre Stocker, Mourad Mekaouche, Zineb Leulmi, Aicha Mechakra, Sophie Thétiot-Laurent, Marcel Culcasi, Sylvia Pietri
ETHNOPHARMACOLOGICAL RELEVANCE: According to Saharian traditional medicine, Anvillea radiata Coss. & Dur. (Asteraceae) has been valued for treating a variety of ailments such as gastro-intestinal, liver and pulmonary diseases, and has gained awareness for its beneficial effect on postprandial hyperglycemia. However, to best of our knowledge, no detailed study of the antidiabetic curative effects of this plant has been conducted yet. AIM OF THE STUDY: To determine the hypoglycemic and antidiabetic effect of dietary supplementation with Anvillea radiata extracts on high-fat-diet (HFD)-induced obesity and insulin resistance in C57BL/6J mice in relation with antioxidant, anti-inflammatory, pancreatic beta-cells and skeletal muscle protection, and digestive enzyme inhibiting properties...
July 31, 2017: Journal of Ethnopharmacology
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