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Hepatotoxicity

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https://www.readbyqxmd.com/read/28934748/severe-drug-induced-liver-injury-as-an-adverse-drug-event-of-antibiotics-a-case-report-and-review-of-the-literature
#1
Martin Munz, Hans Grummich, Josef Birkmann, Martin Wilhelm, Ulrike Holzgrabe, Fritz Sörgel
Drug-induced liver injury is one of the main reasons for acute liver failure. We report the case of a young patient who experienced a drug-induced liver injury resulting in life-threatening acute liver failure after treatment with different antibiotics (amoxicillin, ciprofloxacin, cefazolin, clindamycin) and acetaminophen, or a combination of these drugs. Moreover, we provide an overview of the hepatotoxic potential of these drugs.
September 22, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28934241/hla-dr7-and-hla-dq2-transgenic-mouse-strains-tested-as-a-model-system-for-ximelagatran-hepatotoxicity
#2
Hanna Lundgren, Klara Martinsson, Karin Cederbrant, Johan Jirholt, Daniel Mucs, Katja Madeyski-Bengtson, Said Havarinasab, Per Hultman
The oral thrombin inhibitor ximelagatran was withdrawn in the late clinical trial phase because it adversely affected the liver. In approximately 8% of treated patients, drug-induced liver injury (DILI) was expressed as transient alanine transaminase (ALT) elevations. No evidence of DILI had been revealed in the pre-clinical in vivo studies. A whole genome scan study performed on the clinical study material identified a strong genetic association between the major histocompatibility complex alleles for human leucocyte antigens (HLA) (HLA-DR7 and HLA-DQ2) and elevated ALT levels in treated patients...
2017: PloS One
https://www.readbyqxmd.com/read/28933122/-hepatotoxicity-of-emodin-based-on-ugt1a1-enzyme-mediated-bilirubin-in-liver-microsomes
#3
Qi Wang, Zhong Dai, Yu-Jie Zhang, Shuang-Cheng Ma
To study the hepatotoxicity of emodin based on bilirubin metabolism mediated by glucuronidation of UGT1A1 enzyme. In this study, three different incubation systems were established by using RLM, HLM, and rUGT1A1, with bilirubin as the substrate. Different concentrations of bilirubin and emodin were added in the incubation systems. The double reciprocal Michaelis equation was drawn based on the total amount of bilirubin glucuronidation. The apparent inhibition constant Ki was then calculated with the slope curve to predict the hepatotoxicity...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28932603/the-protective-effect-of-naringenin-oxime-on-cisplatin-induced-toxicity-in-rats
#4
Ismail Koyuncu, Abdurrahim Kocyigit, Ataman Gonel, Erkan Arslan, Mustafa Durgun
The aim of this study is to examine the protective effect of naringenin-oxime (NOX) on cisplatin-induced major organ toxicity and DNA damage in rats. Thirty-five male Wistar albino rats were equally split into five groups as follows: control (i.p., 0.1 ml of saline), Cis administration (i.p., 7 mg/kg b.w.), NOX treatment (i.p., 20 mg/kg b.w., daily for ten days), Cis + NOX20, and Cis + NOX40 combination (i.p., 20 and 40 mg/kg b.w., daily for ten days). Serum and peripheral blood mononuclear leukocytes (PBMC) were obtained from blood...
2017: Biochemistry Research International
https://www.readbyqxmd.com/read/28932197/antiplasmodial-activity-and-toxicological-assessment-of-curcumin-plga-encapsulated-nanoparticles
#5
Zulaikha A Busari, Kabiru A Dauda, Olajumoke A Morenikeji, Funmilayo Afolayan, Oyetunde T Oyeyemi, Jairam Meena, Debasis Sahu, Amulya K Panda
Curcumin is a polyphenolic pigment isolated from the rhizomes of Curcuma longa (turmeric), a medicinal plant widely used in the ancient Indian and Chinese medicine. The antiplasmodial activity of curcumin is often hampered by its fast metabolism and poor water solubility, thus its incorporation into a delivery system could circumvent this problem. This study aimed to evaluate the in vivo antiplasmodial activity and the toxicity assessment of curcumin incorporated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28931625/pml-is-a-ros-sensor-activating-p53-upon-oxidative-stress
#6
Michiko Niwa-Kawakita, Omar Ferhi, Hassane Soilihi, Morgane Le Bras, Valérie Lallemand-Breitenbach, Hugues de Thé
Promyelocytic leukemia (PML) nuclear bodies (NBs) recruit partner proteins, including p53 and its regulators, thereby controlling their abundance or function. Investigating arsenic sensitivity of acute promyelocytic leukemia, we proposed that PML oxidation promotes NB biogenesis. However, physiological links between PML and oxidative stress response in vivo remain unexplored. Here, we identify PML as a reactive oxygen species (ROS) sensor. Pml(-/-) cells accumulate ROS, whereas PML expression decreases ROS levels...
September 20, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28930143/ginseng-for-liver-injury-friend-or-foe
#7
REVIEW
Tae-Woo Kim
Panax sp., including Panax ginseng Meyer, Panax quiquifolius L., or Panax notoginseng (Burk.) FH Chen, have been used as functional foods or for traditional Chinese medicine for diabetes, inflammation, stress, aging, hepatic injury, and cancer. In recent decades, a number of both in vitro and in vivo experiments as well as human studies have been conducted to investigate the efficacy and safety of various types of ginseng samples and their components. Of these, the hepatoprotective and hepatotoxic effects of ginseng and their ginsenosides and polysaccharides are reviewed and summarized...
December 17, 2016: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28929775/hypersensitivity-to-azathioprine-in-a-patient-with-crohn-s-disease-a-case-report
#8
Mafalda Sousa, Luísa Proença, João Carvalho
Azathioprine (AZA) is commonly used in inflammatory bowel disease and many other medical diseases. The most common adverse events of AZA include gastrointestinal effects, hepatotoxicity, myelotoxicity and pancreatitis.
September 18, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28926121/new-pediatric-percentiles-of-liver-enzyme-serum-levels-alt-ast-ggt-effects-of-age-sex-bmi-and-pubertal-stage
#9
Sarah Bussler, Mandy Vogel, Diana Pietzner, Kristian Harms, Theresa Buzek, Melanie Penke, Norman Händel, Antje Körner, Ulrich Baumann, Wieland Kiess, Gunter Flemming
The present study aims to clarify the effects of sex, age, BMI and puberty on transaminase serum levels in children and adolescents and to provide new age- and sex-related percentiles for alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (GGT). Venous blood and anthropometric data were collected from 4,126 cases. Excluded were cases of participants with potential hepatotoxic medication, with evidence of potential illness at the time of blood sampling and non-normal BMI (BMI < 10(th) or > 90(th) )...
September 19, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28923507/pentagalloylglucose-a-highly-bioavailable-polyphenolic-compound-present-in-cortex-moutan-efficiently-blocks-hepatitis-c-virus-entry
#10
Patrick Behrendt, Paula Perin, Nicolas Menzel, Dominic Banda, Stephanie Pfaender, Marco P Alves, Volker Thiel, Phillip Meulemann, Che C Colpitts, Luis M Schang, Florian W R Vondran, Anggakusuma, Michael P Manns, Eike Steinmann, Thomas Pietschmann
Approximately 142 million people worldwide are infected with hepatitis C virus (HCV). Although potent direct acting antivirals are available, high costs limit access to treatment. Chronic hepatitis C virus infection remains a major cause of orthotopic liver transplantation. Moreover, re-infection of the graft occurs regularly. Antivirals derived from natural sources might be an alternative and cost-effective option to complement therapy regimens for global control of hepatitis C virus infection. We tested the antiviral properties of a mixture of different Chinese herbs/roots named Zhi Bai Di Huang Wan (ZBDHW) and its individual components on HCV...
September 15, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28923496/deficiency-of-the-mitochondrial-nad-kinase-causes-stress-induced-hepatic-steatosis-in-mice
#11
Kezhong Zhang, Hyunbae Kim, Zhiyao Fu, Yining Qiu, Zhao Yang, Jiemei Wang, Deqiang Zhang, Xin Tong, Lei Yin, Jing Li, Jianmei Wu, Nathan R Qi, Sander M Houten, Ren Zhang
BACKGROUND & AIMS: The mitochondrial nicotinamide adenine dinucleotide (NAD) kinase (NADK2, also called MNADK) catalyzes phosphorylation of NAD to yield NADP. Little is known about the functions of mitochondrial NADP and MNADK in liver physiology and pathology. We investigated the effects of reduced mitochondrial NADP by deleting MNADK in mice. METHODS: We generated MNADK-knockout (KO) mice on a C57BL/6NTac background; mice with a wild-type Mnadk gene were used as controls...
September 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28922728/hepatoprotective-effect-of-fraxin-against-carbon-tetrachloride-induced-hepatotoxicity-in-vitro-and-in-vivo-through-regulating-hepatic-antioxidant-inflammation-response-and-the-mapk-nf-%C3%AE%C2%BAb-signaling-pathway
#12
Xiaofeng Niu, Fang Liu, Weifeng Li, Wenbing Zhi, Qing Yao, Jinmeng Zhao, Guoxiang Yang, Xiumei Wang, Lin Qin, Zehong He
Fraxin, a main active component isolated from Cortex Fraxini, possesses a variety of bioactivities. However, there is a research gap in studies related to the hepatoprotective activity of fraxin against carbon tetrachloride (CCl4)-induced liver damage has been rarely studied. Thus, the purpose of this study is to evaluate the protective effect of fraxin against CCl4-induced liver damage in mice as well as in HepG2 cells, in addition to further improve the underlying mechanisms of hepatoprotective effect for fraxin...
September 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28922724/oyster-ostrea-plicatula-gmelin-polysaccharides-intervention-ameliorates-cyclophosphamide-induced-genotoxicity-and-hepatotoxicity-in-mice-via-the-nrf2-are-pathway
#13
Shuting Lin, Gengxin Hao, Min Long, Fei Lai, Qingqin Li, Yongmei Xiong, Yan Tian, Dong Lai
In this study, we explored the protective effects of oyster (Ostrea plicatula Gmelin) polysaccharides (OPS) against genotoxicity and liver injury induced by cyclophosphamide (CP) in BALB/c mice. OPS was administered to mice at doses of 100 and 200mg/kg for 7 consecutive days, then 50mg/kg CP was injected via abdomen. Then mice were sacrificed and samples were collected. Bone marrow micronuclei (MN) and polychromatic erythrocytes (PCE): normochromatic erythrocytes (NCE) ratio were calculated to evaluate CP induced genetic toxicity...
September 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28919358/perfused-human-hepatocyte-microtissues-identify-reactive-metabolite-forming-and-mitochondria-perturbing-hepatotoxins
#14
Cliff Rowe, Mohsen Shaeri, Emma Large, Terri Cornforth, Angela Robinson, Tomasz Kostrzewski, Rowena Sison-Young, Christopher Goldring, Kevin Park, David Hughes
Hepatotoxins cause liver damage via many mechanisms but the formation of reactive metabolites and/or damage to liver mitochondria are commonly implicated. We assess 3D human primary hepatocyte microtissues as a platform for hepatotoxicity studies with reactive metabolite-forming and mitochondria-perturbing compounds. We show that microtissues formed from cryopreserved human hepatocytes had bile canaliculi, transcribed mRNA from genes associated with xenobiotic metabolism and expressed functional cytochrome P450 enzymes...
September 15, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28918601/effects-of-phoxim-induced-hepatotoxicity-on-sd-rats-and-the-protection-of-vitamin-e
#15
Jing Zhang, Wentao Song, Yuecheng Sun, Anshan Shan
Currently, public pay more attention to the adverse effect of organophosphate pesticides on human and animal health and on the environment in developing nations. Vitamin E may protect the hepatocyte and increase the function of liver. The study was to investigate the effects of phoxim-induced hepatotoxicity on Sprague Dawley (SD) rats and the protection of vitamin E. SD rats received by gavage 180 mg kg(-1) (per body weight) of phoxim, 200 mg kg(-1) (per body weight) of vitamin E, and phoxim + vitamin E...
September 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28918038/strategies-for-in%C3%A2-vivo-screening-and-mitigation-of-hepatotoxicity-associated-with-antisense-drugs
#16
Piotr J Kamola, Klio Maratou, Paul A Wilson, Kay Rush, Tanya Mullaney, Tom McKevitt, Paula Evans, Jim Ridings, Probash Chowdhury, Aude Roulois, Ann Fairchild, Sean McCawley, Karen Cartwright, Nigel J Gooderham, Timothy W Gant, Kitty Moores, Stephen A Hughes, Mark R Edbrooke, Kenneth Clark, Joel D Parry
Antisense oligonucleotide (ASO) gapmers downregulate gene expression by inducing enzyme-dependent degradation of targeted RNA and represent a promising therapeutic platform for addressing previously undruggable genes. Unfortunately, their therapeutic application, particularly that of the more potent chemistries (e.g., locked-nucleic-acid-containing gapmers), has been hampered by their frequent hepatoxicity, which could be driven by hybridization-mediated interactions. An early de-risking of this liability is a crucial component of developing safe, ASO-based drugs...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917835/antitumor-activity-pharmacokinetics-tumor-homing-effect-and-hepatotoxicity-of-a-species-cross-reactive-c-met-antibody
#17
Hyunkyu Park, Donggeon Kim, Eunju Son, Sunhwa Shin, Jason K Sa, Seok-Hyung Kim, Yeup Yoon, Do-Hyun Nam
The receptor tyrosine kinase c-Met plays critical roles in promoting tumor growth, invasion, metastasis, and angiogenesis in various types of cancer and is a promising therapeutic target. The development of a species cross-reactive therapeutic antibody could provide useful to comprehensive preclinical assessment in animal models. Towards this goal, we developed human/mouse cross-reactive c-Met antibodies using an antibody phage library. IRCR201, a c-Met antibody with species cross-reactivity, successfully inhibited the HGF/c-Met signaling pathway via degradation of c-Met and disruption of the binding with its partners, and demonstrated strong in vivo antitumor activity...
September 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28914560/thiopurine-metabolite-levels-in-patients-with-atopic-dermatitis-and-or-chronic-hand-foot-eczema-treated-with-azathioprine
#18
F M Garritsen, J van der Schaft, C A F Bruijnzeel-Koomen, R H van Schaik, M de Graaf, M P H van den Broek, M S de Bruin-Weller
BACKGROUND: Azathioprine is frequently used in severe eczema. It is converted in the liver into active metabolites, including 6-thioguanine nucleotide (6-TGN) and methylated 6-methylmercaptopurine (6-MMP). In the past, the therapeutic potential of azathioprine may have not been fully utilized. Recent investigations on inflammatory bowel disease have led to a better understanding of azathioprine metabolism and optimizing treatment. OBJECTIVE: To investigate whether measuring thiopurine metabolites in circulation can improve the effectiveness and safety of azathioprine treatment in patients with atopic dermatitis and/or chronic hand/foot eczema...
September 15, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28912805/antifibrotic-effect-of-lactulose-on-a-methotrexate-induced-liver-injury-model
#19
Banu Taskin, Mümin Alper Erdoğan, Gürkan Yiğittürk, Damla Günenç, Oytun Erbaş
The most severe side effect of prolonged MTX treatment is hepatotoxicity. The aim of this study is to investigate the effect of lactulose treatment on MTX-induced hepatotoxicity in a rat model. Twenty-four male rats were included in the study. Sixteen rats were given a single dose of 20 mg/kg MTX to induce liver injury. Eight rats were given no drugs. 16 MTX-given rats were divided into two equal groups. Group 1 subjects were given lactulose 5 g/kg/day, and group 2 subjects were given saline 1 ml/kg/day for 10 days...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28912098/melatonin-mediated-upregulation-of-sirt3-attenuates-sodium-fluoride-induced-hepatotoxicity-by-activating-the-mt1-pi3k-akt-pgc-1%C3%AE-signaling-pathway
#20
Chao Song, Jiamin Zhao, Beibei Fu, Dan Li, Tingchao Mao, Wei Peng, Haibo Wu, Yong Zhang
Mitochondrial reactive oxygen species (ROS) production has been implicated in the pathogenesis of fluoride toxicity in liver. Melatonin, an indolamine synthesized in the pineal gland, was previously shown to protect against sodium fluoride (NaF)-induced hepatotoxicity. This study investigated the protective effects of melatonin pretreatment on NaF-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. Reducing mitochondrial ROS by melatonin substantially attenuated NaF-induced NADPH oxidase 4 (Nox4) upregulation and cytotoxicity in L-02 cells...
September 11, 2017: Free Radical Biology & Medicine
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