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Drug-induced hepatotoxicity

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https://www.readbyqxmd.com/read/28717109/utility-of-human-hepatocyte-spheroids-without-feeder-cells-for-evaluation-of-hepatotoxicity
#1
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/28717103/metabolomics-of-an-in-vitro-liver-model-containing-primary-hepatocytes-assembling-around-an-endothelial-cell-network-comparative-study-on-the-metabolic-stability-and-the-effect-of-acetaminophen-treatment
#2
Yu Toyoda, Kasumi Kashikura, Tomoyoshi Soga, Yoh-Ichi Tagawa
Recently, a novel culture system consisting of primary hepatocytes structured over a network of endothelial cells on the Engelbreth-Holm-Swarm (EHS) gel has been reported. This in vitro liver model on the EHS gel (IVLEHS) has been shown to maintain the expression of hepatic genes and their functional activity. Moreover, the IVLEHS was more sensitive to xenobiotics than hepatocyte monocultures, suggesting the potential utility of this culture system for compound hepatotoxicity screening. However, the effect of this three-dimensional structure formation on the cellular metabolic profile of hepatocytes in the IVLEHS is not well understood...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28713372/nanoparticle-formulated-curcumin-prevents-posttherapeutic-disease-reactivation-and-reinfection-with-mycobacterium-tuberculosis-following-isoniazid-therapy
#3
Sultan Tousif, Dhiraj Kumar Singh, Sitabja Mukherjee, Shaheer Ahmad, Rakesh Arya, Ranjan Nanda, Anand Ranganathan, Maitree Bhattacharyya, Luc Van Kaer, Santosh K Kar, Gobardhan Das
Curcumin, the bioactive component of turmeric also known as "Indian Yellow Gold," exhibits therapeutic efficacy against several chronic inflammatory and infectious diseases. Even though considered as a wonder drug pertaining to a myriad of reported benefits, the translational potential of curcumin is limited by its low systemic bioavailability due to its poor intestinal absorption, rapid metabolism, and rapid systemic elimination. Therefore, the translational potential of this compound is specifically challenged by bioavailability issues, and several laboratories are making efforts to improve its bioavailability...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28710607/evaluation-of-a-food-and-drug-administration-mandate-to-limit-acetaminophen-in-prescription-combination-products
#4
David Goldberger, David Vearrier
INTRODUCTION: In 2014, the US Food and Drug Administration limited the production of prescription acetaminophen-opioid combination products to 325 mg per dose unit. The goal of this mandate was to decrease the likelihood of unintentional acetaminophen hepatotoxicity. This study was designed to determine if this federal regulation has succeeded in reducing unintentional acetaminophen-induced hepatotoxicity from opioid combination products. METHODS: Using data from the National Poison Data System (NPDS), we analyzed all calls to US Poison Control Centers in the years 2013 and 2015 for acetaminophen-opioid combination product exposures...
July 14, 2017: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
https://www.readbyqxmd.com/read/28702139/ramipril-associated-cholestasis-in-the-setting-of-recurrent-drug-induced-liver-injury
#5
David Forner, Tasha Kulai, Thomas Arnason, Steven E Gruchy, Magnus MacLeod
Aim: Angiotensin-converting enzyme inhibitors (ACEIs) are commonly used to treat hypertension. Although generally well tolerated, the adverse effects of ACEIs include hypotension, cough, acute kidney injury and hyperkalemia. Rare reports of ACEI-induced hepatotoxicity have been described, most notably a cholestatic pattern of injury related to captopril. A 67-year-old male presented to the emergency department with a three-week history of jaundice, pruritis and weakness. Eight weeks before, he began taking ramipril and clopidogrel...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28699415/a-scalable-approach-for-the-generation-of-human-pluripotent-stem-cell-derived-hepatic-organoids-with-sensitive-hepatotoxicity-features
#6
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/28691103/role-of-nonalcoholic-fatty-liver-disease-as-risk-factor-for-drug-induced-hepatotoxicity
#7
Julie Massart, Karima Begriche, Caroline Moreau, Bernard Fromenty
BACKGROUND: Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. AIM: The main objective of the present review was to collect the available information regarding the role of NAFLD as risk factor for drug-induced hepatotoxicity...
February 2017: Journal of Clinical and Translational Research
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
#8
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/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
#9
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/28685675/the-beneficial-effects-of-sulfur-containing-amino-acids-on-cisplatin-induced-cardiotoxicity-and-neurotoxicity-in-rodents
#10
Gvozden Rosic, Jovana Joksimovic, Dragica Selakovic, Vladimir Jakovljevic, Vladimir Zivkovic, Ivan Srejovic, Marko Djuric, Dragan Djuric
Cisplatin is one the most frequently used chemotherapeutic drugs for several decades. Although its antineoplastic effect has been reported in treatment of numerous malignances, various adverse effects seem to be the crucial limiting factor for its administration. Beside the most commonly described nephro- and hepatotoxicity, cisplatin therapy is also accompanied with gastrointestinal, reproductive, hematological, cardiovascular and neurological side effects. Since it has been reported that cisplatin induce oxidative damage in various tissues (by means of altered ROS production, as well as by depletion of antioxidants), it seems reasonable that huge efforts had been put in the investigations of antioxidant supplementation as potential therapeutical approach for attenuation of cisplatin toxicities...
July 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28682524/restorative-effects-of-chrysin-pretreatment-on-oxidant-antioxidant-status-inflammatory-cytokine-production-and-apoptotic-and-autophagic-markers-in-acute-paracetamol-induced-hepatotoxicity-in-rats-an-experimental-and-biochemical-study
#11
Eyup Eldutar, Fatih Mehmet Kandemir, Sefa Kucukler, Cuneyt Caglayan
Paracetamol (PC) is a widely used analgesic and antipyretic drug, but it leads to acute hepatotoxicity at high doses intakes. This study was aimed to investigate the effects of Chrysin (CR) on hepatotoxicity constituted at high doses of PC in rats. Rats were subjected to oral pretreatment of CR (25 and 50 mg/kg b.w.) via feeding needle for 6 days against hepatotoxicity induced by a single dose of PC (500 mg/kg b.w.) administered orally via feeding needles. Although PC increases lipid peroxidation and liver enzyme activities, it has led to reduction of antioxidant enzyme activities...
July 6, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28677736/glutathione-peroxidase-3-is-a-protective-factor-against-acetaminophen%C3%A2-induced-hepatotoxicity-in-vivo-and-in-vitro
#12
Syu-Ichi Kanno, Ayako Tomizawa, Shin Yomogida, Akiyoshi Hara
Acetaminophen (APAP) is a widely available antipyretic and analgesic; however, overdose of the drug inflicts severe damage to the liver. It is well established that the hepatotoxicity of APAP is initiated by formation of a reactive metabolite, N‑acetyl‑p‑benzoquinone imine (NAPQI), which can be detoxified by conjugation with reduced glutathione (GSH), a typical antioxidant. We recently found that the blood mRNA expression level of glutathione peroxidase 3 (Gpx3), which catalyzes the oxidation of GSH, is associated with the extent of APAP‑induced hepatotoxicity in mice...
July 3, 2017: International Journal of Molecular Medicine
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
#13
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/28671602/mechanism-investigation-of-rifampicin-induced-liver-injury-using-comparative-toxicoproteomics-in-mice
#14
Ju-Hyun Kim, Woong Shik Nam, Sun Joo Kim, Oh Kwang Kwon, Eun Ji Seung, Jung Jae Jo, Riya Shresha, Tae Hee Lee, Tae Won Jeon, Sung Hwan Ki, Hye Suk Lee, Sangkyu Lee
Tuberculosis is one of the top causes of death among curable infectious diseases; it is an airborne infectious disease that killed 1.1 million people worldwide in 2010. Anti-tuberculosis drug-induced liver injury is the primary cause of drug-induced liver injury (DILI). Rifampicin is one of the most common anti-tuberculosis therapies and has well-known hepatotoxicity. To understand the mechanism of rifampicin-induced liver injury, we performed a global proteomic analysis of liver proteins by LC-MS/MS in a mouse model after the oral administration of 177 and 442...
July 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28670513/in-vitro-generated-hepatocyte-like-cells-a-novel-tool-in-regenerative-medicine-and-drug-discovery
#15
REVIEW
Kobra Zakikhan, Behshad Pournasr, Massoud Vosough, Marjan Nassiri-Asl
Hepatocyte-like cells (HLCs) are generated from either various human pluripotent stem cells (hPSCs) including induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), or direct cell conversion, mesenchymal stem cells as well as other stem cells like gestational tissues. They provide potential cell sources for biomedical applications. Liver transplantation is the gold standard treatment for the patients with end stage liver disease, but there are many obstacles limiting this process, like insufficient number of donated healthy livers...
July 2017: Cell Journal
https://www.readbyqxmd.com/read/28668488/glycyrrhetinic-acid-prevents-acetaminophen-induced-acute-liver-injury-via-the-inhibition-of-cyp2e1-expression-and-hmgb1-tlr4-signal-activation-in-mice
#16
Genling Yang, Li Zhang, Li Ma, Rong Jiang, Ge Kuang, Ke Li, Hongtao Tie, Bin Wang, Xinyu Chen, Tianjun Xie, Xia Gong, Jingyuan Wan
Acetaminophen (APAP) is a widely used antipyretic and analgesic drug, which is safe and effective at the therapeutic dose. Unfortunately, excessive dosage of APAP could cause severe liver injury due to lack of effective therapy. Successful therapeutic strategies are urgently requested in clinic. Glycyrrhetinic acid (GA), derived from a traditional medicine licorice, has been shown to exert anti-inflammatory and antioxidant actions. In this study, the effect and the underlying mechanism of GA on APAP-induced hepatotoxicity were explored...
June 29, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28659801/hepatocellular-toxicity-associated-with-tyrosine-kinase-inhibitors-mitochondrial-damage-and-inhibition-of-glycolysis
#17
Franziska Paech, Jamal Bouitbir, Stephan Krähenbühl
Tyrosine kinase inhibitors (TKIs) are anticancer drugs with a lesser toxicity than classical chemotherapeutic agents but still with a narrow therapeutic window. While hepatotoxicity is known for most TKIs, underlying mechanisms remain mostly unclear. We therefore aimed at investigating mechanisms of hepatotoxicity for imatinib, sunitinib, lapatinib and erlotinib in vitro. We treated HepG2 cells, HepaRG cells and mouse liver mitochondria with TKIs (concentrations 1-100 μM) for different periods of time and assessed toxicity...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28658959/vitamin-c-attenuates-methotrexate-induced-oxidative-stress-in-kidney-and-liver-of-rats
#18
M Savran, E Cicek, D K Doguc, H Asci, S Yesilot, I A Candan, B Dagdeviren, F N Cankara, M Oncu, A C Uğuz, M K Ozer
Like several other anticancer drugs, methotrexate (MTX) causes side effects, such as neuropathic pain, hepatotoxicity, and nephrotoxicity. Abnormal production of reactive oxygen species has been suspected in the pathophysiology of MTX-induced hepatorenal toxicity. Therefore, the aim of this study was to investigate the probable protective role of vitamin C (Vit C) on oxidative stress induced by MTX in the liver and kidney tissues of rats. A total of 32 rats were randomly and equally divided into four groups...
June 29, 2017: Physiology International
https://www.readbyqxmd.com/read/28655703/in-vitro-antioxidant-hepatoprotective-potential-and-chemical-profiling-of-syzygium-aromaticum-using-hplc-and-gc-ms
#19
Saman Hina, Khalilur Rehman, Muhammad Shahid, Nazish Jahan
The objective of the present study was to evaluate the in vitro antioxidant and hepatoprotective potential of Syzygium aromaticum (clove) against CCl4-induced hepatotoxicity using rat liver slice culture (LSC) model. Antioxidant activity in terms of DPPH radical scavenging activity and ferric reducing antioxidant power (FRAP) of different concentrations of S. aromaticum was in the range of 41.01-90.33% and 138.15-595.63 Fe (II) mg/mL, respectively. Plasmid pBR322 DNA protection activity was observed with all three concentrations of S...
May 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28651233/terminalia-bellirica-gaertn-roxb-fruit-mitigates-ccl4-induced-oxidative-stress-and-hepatotoxicity-in-rats
#20
Jayesh Kuriakose, Helen Lal Raisa, Vysakh A, Binil Eldhose, Latha M S
Terminalia bellirica (Gaertn.) Roxb. is a medicinal plant used for the treatment of various ailments in the traditional system of medicine like Ayurveda where it has been prescribed as a rejuvenator and general health tonic. The fruit of the plant is one of the components of the age old ayurvedic formulation-'Triphala'. The present study evaluates curative effect of aqueous acetone extract of Terminalia bellirica fruits (AATB) against CCl4 induced oxidative stress and liver damage in an animal model. Two doses of the fruit extract (200mg/kg body weight and 400mg/kg body weight) were investigated for the beneficial effects...
June 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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