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Drug-induced hepatotoxicity

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https://www.readbyqxmd.com/read/27909995/solithromycin-a-novel-fluoroketolide-for-the-treatment-of-community-acquired-bacterial-pneumonia
#1
REVIEW
George G Zhanel, Erika Hartel, Heather Adam, Sheryl Zelenitsky, Michael A Zhanel, Alyssa Golden, Frank Schweizer, Bala Gorityala, Philippe R S Lagacé-Wiens, Andrew J Walkty, Alfred S Gin, Daryl J Hoban, Joseph P Lynch, James A Karlowsky
Solithromycin is a novel fluoroketolide developed in both oral and intravenous formulations to address increasing macrolide resistance in pathogens causing community-acquired bacterial pneumonia (CABP). When compared with its macrolide and ketolide predecessors, solithromycin has several structural modifications which increase its ribosomal binding and reduce its propensity to known macrolide resistance mechanisms. Solithromycin, like telithromycin, affects 50S ribosomal subunit formation and function, as well as causing frame-shift errors during translation...
December 1, 2016: Drugs
https://www.readbyqxmd.com/read/27901623/autotransplantation-of-spleen-mitigates-drug-induced-liver-damage-in-splenectomized-mice
#2
Sabrine Teixeira Ferraz Grunewald, Alice Belleigoli Rezende, Bárbara Bruna Muniz Figueiredo, Ana Carolina de Paula Mendonça, Caroline de Souza Almeida, Erick Esteves de Oliveira, Flávia de Paoli, Henrique Couto Teixeira
PURPOSE: The spleen presents numerous functions, including the production of immunoglobulins and blood filtration, removing microorganisms and cellular debris. The spleen also has anatomical and functional relationship with the liver, but there are few studies on this topic. The aim of this study was to assess the effect of splenectomy and autologous spleen transplantation on both filtering functions of spleen and acetaminophen-induced hepatotoxicity. MATERIALS AND METHODS: Fifty-two BALB/c mice were randomized into four groups: splenectomized; splenectomy and splenic autotransplantation in the greater omentum; sham operated control; and non-operated control...
November 30, 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
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
#3
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
#4
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/27865386/factors-associated-with-anti-tb-drug-induced-hepatotoxicity-and-genetic-polymorphisms-in-indigenous-and-non-indigenous-populations-in-brazil
#5
Melissa M Heinrich, Verônica M Zembrzuski, Marcos M Ota, Flavia P Sacchi, Raquel L F Teixeira, Pedro H Cabello Acero, Geraldo Marcelo Cunha, Reinaldo Souza-Santos, Julio Croda, Paulo C Basta
Anti-tuberculosis (TB) drugs are responsible for the occurrence of several adverse drug reactions (ADRs), including hepatotoxicity. The aim was to estimate the incidence of hepatotoxicity and its association with genetic polymorphisms and clinical-epidemiological factors by comparing indigenous and non-indigenous TB patients. We investigated clinical-epidemiological variables, serum levels of liver enzymes and NAT2, CYP2E1 and GSTM1 polymorphisms. A non-conditional logistic regression was used to identify the factors associated with hepatotoxicity...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27865233/cyp2e1-polymorphism-acetylator-profiles-and-drug-induced-liver-injury-incidence-of-indonesian-tuberculosis-patients
#6
Dyah A Perwitasari, Lalu M Irham, Endang Darmawan, Ully A Mulyani, J Atthobari
OBJECTIVE: A polymorphism of CYP2E1 may be directly associated with the development of INH hepatotoxicity. We conducted this study to evaluate the association between polymorphisms of CYP2E1, Isoniazid (INH) concentration and the acetylator status of INH in cases of Indonesian tuberculosis patients with drug-induced liver disease (DILI). METHODS: We conducted our study with a cohort design consisting of 55 Indonesian adult tuberculosis (TB) patients. Acetylating phenotypes were studied in using the metabolic ratio of plasma AcHZ/HZ...
July 2016: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/27862262/different-effects-of-selective-%C3%AE-1-adrenoceptor-antagonists-nebivolol-or-atenolol-in-acetaminophen-induced-heptatotoxicity-of-rats
#7
Remon R Rofaeil, Maha Yehia Kamel, Walaa Yehia Abdelzaher
Acetaminophen (APAP) overdose is a common cause of acute liver failure and beta blockers are commonly used drugs in clinical practice. This study aims to evaluate the effect of two different beta blockers agents as nebivolol and atenolol against APAP-induced hepatotoxicity. Male wistar rats were treated with APAP (2 g/kg/day, p.o.) to induce hepatotoxicity. Our results showed that nebivolol and atenolol reduced heart rate and blood pressure. Nebivolol (5 mg/kg /day, p.o.) for 14 days has a hepatoprotective effect shown by significant decrease in hepatic injury parameters (serum AST and ALT) with significant suppression of hepatic malondialdehyde (MDA) and nitric oxide (NO) which were elevated with APAP administration...
November 14, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27860156/hepatotoxicity-of-statins-and-other-lipid-lowering-agents
#8
REVIEW
Einar S Björnsson
Statins are generally well tolerated and adverse effects are relatively rare. Clinical trials are underpowered to detect uncommon adverse effects such as idiosyncratic drug-induced liver injury. This review is aimed at covering the current knowledge on the hepatotoxicity associated with statins and other lipid lowering drugs. Both atorvastatin and simvastatin have been associated with more than 50 case reports of liver injury and other statins have been implicated in this type of liver injury as well. Idiosyncratic liver injury due to statins has been reported to occur 1...
November 8, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
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
#9
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/27847016/low-prevalence-of-hepatitis-b-and-c-among-tuberculosis-patients-in-duhok-province-kurdistan-are-hbsag-and-anti-hcv-prerequisite-screening-parameters-in-tuberculosis-control-program
#10
Muayad A Merza, Safer M Haji, Abid Mohialdeen Hasan Alsharafani, Shivan U Muhammed
OBJECTIVE/BACKGROUND: Viral hepatitis, particularly hepatitis B virus (HBV) and hepatitis C virus (HCV), infections and tuberculosis (TB) are a global public health concern. Co-infection with HBV or HCV among TB patients may potentiate the risk of hepatotoxicity induced by anti-TB drugs. Hence, the aim of this study was to identify the prevalence of HBV and HCV among TB patients included in the Duhok National Tuberculosis Program (NTP). METHODS: The Duhok NTP Center is a specialized institution in Duhok City, Iraq, concerned with management and follow-up of TB patients...
September 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/27842778/drug-induced-hepatotoxicity%C3%A2-a-topic-where-we-don-t-know-enough
#11
EDITORIAL
Vinod K Rustgi
No abstract text is available yet for this article.
February 2017: Clinics in Liver Disease
https://www.readbyqxmd.com/read/27842777/phenotypes-and-pathology-of-drug-induced-liver-disease
#12
REVIEW
Zachary D Goodman
Drug hepatotoxicity can simulate nearly any clinical syndrome or pathologic lesion that may occur in the liver, so clinical and histopathologic diagnosis of drug-induced liver injury may be difficult. Nevertheless, most drugs that are known to idiosyncratic liver injury tend to cause patterns of injury that produce characteristic phenotypes. Recognition of these patterns or phenotypes in liver biopsy material is helpful in evaluation of clinical cases of suspected drug-induced liver injury.
February 2017: Clinics in Liver Disease
https://www.readbyqxmd.com/read/27842775/epidemiology-and-genetic-risk-factors-of-drug-hepatotoxicity
#13
REVIEW
Jawad Ahmad, Joseph A Odin
Idiosyncratic drug-induced liver injury (DILI) from prescription medications and herbal and dietary supplements has an annual incidence rate of approximately 20 cases per 100,000 per year. However, the risk of DILI varies greatly according to the drug. In the United States and Europe, antimicrobials are the commonest implicated agents, with amoxicillin/clavulanate the most common, whereas in Asian countries, herbal and dietary supplements predominate. Genetic analysis of DILI is currently limited, but multiple polymorphisms of human leukocyte antigen genes and genes involved in drug metabolism and transport have been identified as risk factors for DILI...
February 2017: Clinics in Liver Disease
https://www.readbyqxmd.com/read/27842774/mechanisms-of-drug-induced-hepatotoxicity
#14
REVIEW
Amina Ibrahim Shehu, Xiaochao Ma, Raman Venkataramanan
Drug-induced hepatotoxicity (DIH) is a significant cause of acute liver failure and liver transplantation. Diagnosis is challenging due to the idiosyncratic nature, its presentation in the form of other liver disease, and the lack of a definite diagnostic criteria. Generation of reactive metabolites, oxidative stress, and mitochondrial dysfunction are common mechanisms involved in DIH. Certain risk factors associated with a drug and within an individual further predispose patients to DIH.
February 2017: Clinics in Liver Disease
https://www.readbyqxmd.com/read/27842770/management-of-acute-hepatotoxicity-including-medical-agents-and-liver-support-systems
#15
REVIEW
Humberto C Gonzalez, Syed-Mohammed Jafri, Stuart C Gordon
Drug-induced liver injury (DILI) can be predictable or idiosyncratic and has an estimated incidence of approximately 20 cases per 100,000 persons per year. DILI is a common cause of acute liver failure in the United States. No accurate tests for diagnosing DILI exist, and its diagnosis is based on exclusion of other conditions. Managing DILI includes discontinuing the suspected causative agent and in selected cases administering an antidote. Liver support systems are used for long-term support or as a bridge to transplantation and are effective for improving encephalopathy, hyperbilirubinemia, and other liver-related conditions, but whether they improve survival remains uncertain...
February 2017: Clinics in Liver Disease
https://www.readbyqxmd.com/read/27842766/drug-hepatotoxicity-environmental-factors
#16
REVIEW
Jonathan G Stine, Naga P Chalasani
Drug-induced liver injury presents as various forms of acute and chronic liver disease. There is wide geographic variation in the most commonly implicated agents. Smoking can induce cytochrome P450 enzymes but this does not necessarily translate into clinically relevant drug-induced liver injury. Excessive alcohol consumption is a clear risk factor for intrinsic hepatotoxicity from acetaminophen and may predispose to injury from antituberculosis medications. Understanding of the role of infection, proinflammatory states, disorders of coagulation, and the hepatic clock in predisposing patients to drug-induced liver injury is evolving...
February 2017: Clinics in Liver Disease
https://www.readbyqxmd.com/read/27835982/effectiveness-of-hepatoprotective-drugs-for-anti-tuberculosis-drug-induced-hepatotoxicity-a-retrospective-analysis
#17
Zenya Saito, Yugo Kaneko, Akira Kinoshita, Yusuke Kurita, Kyuto Odashima, Tsugumi Horikiri, Yutaka Yoshii, Aya Seki, Yoshitaka Seki, Hiroshi Takeda, Kazuyoshi Kuwano
BACKGROUND: The effectiveness of hepatoprotective drugs for DIH (drug induced hepatotoxicity) during tuberculosis treatment is not clear. We evaluated the effectiveness of hepatoprotective drugs by comparing the period until the normalization of hepatic enzymes between patients who were prescribed with the hepatoprotective drugs after DIH was occurred and patients who were not prescribed with the hepatoprotective drugs. METHODS: During 2006-2010, 389 patients with active tuberculosis were included in this study...
November 11, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27832320/activation-of-nuclear-receptor-car-by-an-environmental-pollutant-perfluorooctanoic-acid
#18
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/27830547/propagation-of-human-hepatocytes-in-upa-scid-mice-producing-chimeric-mice-with-humanized-liver
#19
Hiroki Ohshita, Chise Tateno
Primary or cryopreserved human hepatocytes (h-heps) have been used as the gold standard for in vitro metabolism and hepatotoxicity studies; however, the supply of h-heps is limited and they cannot grow in vitro. We achieved approximately 1000-fold propagation of h-heps in the liver of albumin promoter/enhancer-driven urokinase-type plasminogen activator transgenic/severe combined immunodeficiency disease (uPA/SCID) mice with genetically induced liver disease and immunodeficiency. When h-heps are transplanted into the uPA/SCID mouse liver via the spleen, the h-heps engraft in the mouse liver, resulting in its repopulation with h-heps...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27826632/inhibition-of-pannexin1-channels-alleviates-acetaminophen-induced-hepatotoxicity
#20
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
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