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Drug induced liver injury

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https://www.readbyqxmd.com/read/28429935/saponins-ginsenosides-from-the-leaves-of-panax-quinquefolius-ameliorated-acetaminophen-induced-hepatotoxicity-in-mice
#1
Xingyue Xu, Junnan Hu, Zhi Liu, Rui Zhang, Yufang He, Wei Hou, Zhiqing Wang, Ge Yang, Wei Li
Acetaminophen (APAP) overdose is the most frequent inducement of drug-induced acute liver injury (ALI). The purpose of this study was to investigate the protective effect of saponins (ginsenosides) from the leaves of Panax quinquefolius (PQS) against APAP-induced hepatotoxicity and the involved mechanism were investigated. Mice were pretreated with PQS (150 and 300 mg/kg) by oral gavage for seven days before being treated with 250 mg/kg APAP. Sever liver injury was exerted at 24 h post-APAP and hepatotoxicity was assessed...
April 21, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28425415/drug-induced-liver-injury-at-a-tertiary-hospital-in-india-etiology-clinical-features-and-predictors-of-mortality
#2
Chetan Rathi, Nirav Pipaliya, Ruchir Patel, Meghraj Ingle, Aniruddha Phadke, Prabha Sawant
INTRODUCTION AND AIMS: Drug-induced liver injury (DILI) is rare; however, it is one of the important causes of acute liver failure which results in significant morbidity or mortality. MATERIAL AND METHODS: Patients with suspected DILI were enrolled based on predefined criteria and followed up for at least 6 months or until normalization of liver tests. Causality assessment was done by applying the Roussel Uclaf Causality Assessment Method model. RESULTS: We collected data from 82 individuals diagnosed with DILI at our hospital from 2014 through 2015 (41 men; median age, 38 years)...
May 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28425350/metabolomics-approach-discriminates-toxicity-index-of-pyrazinamide-and-its-metabolic-products-pyrazinoic-acid-and-5-hydroxy-pyrazinoic-acid
#3
A Rawat, S Chaturvedi, A K Singh, A Guleria, D Dubey, A K Keshari, V Raj, A Rai, A Prakash, U Kumar, D Kumar, S Saha
Pyrazinamide (PYZ)-an essential component of primary drug regimen used for the treatment and management of multidrug resistant or latent tuberculosis-is well known for its hepatoxicity. However, the mechanism of PYZ-induced hepatotoxicity is still unknown to researchers. Studies have shown that the drug is metabolized in the liver to pyrazinoic acid (PA) and 5-hydroxy pyrazinoic acid (5-OHPA) which individually may cause different degrees of hepatotoxicity. To evaluate this hypothesis, PYZ, PA, and 5-OHPA were administered to albino Wistar rats orally (respectively, at 250, 125, and 125 mg kg(-1) for 28 days)...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28419467/refining-liver-safety-risk-assessment-application-of-mechanistic-modeling-and-serum-biomarkers-to-cimaglermin-alfa-ggf2-clinical-trials
#4
Diane M Longo, Grant T Generaux, Brett A Howell, Scott Q Siler, Daniel J Antoine, Donald Button, Anthony Caggiano, Andrew Eisen, Jennifer Iaci, Ric Stanulis, Tom Parry, Merrie Mosedale, Paul B Watkins
Cimaglermin alfa (GGF2) is a recombinant human protein growth factor in development for heart failure. Phase 1 trials were suspended when 2 cimaglermin alfa-treated subjects experienced concomitant elevations in serum aminotransferases and total bilirubin meeting current FDA criteria for a serious liver safety signal (i.e. "Hy's Law"). We assayed mechanistic biomarkers in archived clinical trial serum samples which confirmed the hepatic origin of the aminotransferase elevations in these two subjects and identified apoptosis as the major mode of hepatocyte death...
April 17, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28417920/evaluation-of-the-potential-risk-of-drugs-to-induce-hepatotoxicity-in-human-relationships-between-hepatic-steatosis-observed-in-non-clinical-toxicity-study-and-hepatotoxicity-in-humans
#5
Keisuke Goda, Akio Kobayashi, Akemi Takahashi, Tadakazu Takahashi, Kosuke Saito, Keiko Maekawa, Yoshiro Saito, Shoichiro Sugai
In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury (DILI) in humans...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28413320/panax-ginseng-meyer-prevents-radiation-induced-liver-injury-via-modulation-of-oxidative-stress-and-apoptosis
#6
Hyeong-Geug Kim, Seong-Soon Jang, Jin-Seok Lee, Hyo-Seon Kim, Chang-Gue Son
BACKGROUND: Radiotherapy is one of the most important modalities in cancer treatment; however, normal tissue damage is a serious concern. Drug development for the protection or reduction of normal tissue damage is therefore a clinical issue. Herein, we evaluated the protective properties of Panax ginseng Meyer and its corresponding mechanisms. METHODS: C56BL/6 mice were orally pretreated with P. ginseng water extract (PGE; 25 mg/kg, 50 mg/kg, or 100 mg/kg) or intraperitoneally injected melatonin (20 mg/kg) for 4 d consecutively, then exposed to 15-Gy X-ray radiation 1 h after the last administration...
April 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28412648/content-decline-of-serca-inhibitors-saikosaponin-a-and-d-attenuates-cardiotoxicity-and-hepatotoxicity-of-vinegar-baked-radix-bupleuri
#7
Shifeng Wang, Yuxin Zhang, Qiao Zhang, Sha Peng, Chen Shen, Yangyang Yu, Minyu Zhang, Wei Yang, Qinghua Wu, Yanling Zhang, Shiyou Li, Yanjiang Qiao
Improper usage of unprocessed Radix bupleuri root (chaihu) may cause cardiotoxicity and liver injury. Baking herb with vinegar is believed to attenuate the adverse responses. However, the chemical and molecular basis involved remained unclear. To this end, we investigated the in vitro toxicity of saikosaponin a, c, d, and their hydrolysates saikosaponin b1 and b2. Results showed that SSa and SSd possessed higher affinity with sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) by molecular docking, and exhibited stronger toxic responses on cardiomyocytes and hepatocytes than the other three saikosaponins in equivalent concentrations...
April 4, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28411363/animal-models-of-alcoholic-liver-disease-pathogenesis-and-clinical-relevance
#8
Bin Gao, Ming-Jiang Xu, Adeline Bertola, Hua Wang, Zhou Zhou, Suthat Liangpunsakul
Alcoholic liver disease (ALD), a leading cause of chronic liver injury worldwide, comprises a range of disorders including simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Over the last five decades, many animal models that have been useful for the study of ALD pathogenesis have been developed. Recently, a chronic-plus-binge ethanol feeding model was reported. This model induces significant steatosis, hepatic neutrophil infiltration, and liver injury. A clinically relevant model of high-fat diet feeding plus binge ethanol was also developed, which highlights the risk of excessive binge drinking in obese/overweight individuals...
April 14, 2017: Gene Expression
https://www.readbyqxmd.com/read/28407580/isoalantolactone-inhibits-lps-induced-inflammation-via-nf-%C3%AE%C2%BAb-inactivation-in-peritoneal-macrophages-and-improves-survival-in-sepsis
#9
Guodong He, Xu Zhang, Yanhua Chen, Jing Chen, Li Li, Yubo Xie
Sepsis, a clinical syndrome occurring in patients following infection or injury, is a leading cause of mortality worldwide. It involves uncontrolled inflammatory response resulting in multi-organ failure and even death. Isoalantolactone (IAL), a sesquiterpene lactone, is known for its anti-cancer effects. Nevertheless, little is known about the anti-inflammatory effects of IAL, and the role of IAL in sepsis is unclear. In this study, we demonstrated that IAL decreased lipopolysaccharide (LPS)-mediated production of nitric oxide, PEG2 and cytokines (IL-6, TNF-α) in peritoneal macrophages and RAW 264...
April 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28405790/csh-guidelines-for-the-diagnosis-and-treatment-of-drug-induced-liver-injury
#10
EDITORIAL
Yue-Cheng Yu, Yi-Min Mao, Cheng-Wei Chen, Jin-Jun Chen, Jun Chen, Wen-Ming Cong, Yang Ding, Zhong-Ping Duan, Qing-Chun Fu, Xiao-Yan Guo, Peng Hu, Xi-Qi Hu, Ji-Dong Jia, Rong-Tao Lai, Dong-Liang Li, Ying-Xia Liu, Lun-Gen Lu, Shi-Wu Ma, Xiong Ma, Yue-Min Nan, Hong Ren, Tao Shen, Hao Wang, Ji-Yao Wang, Tai-Ling Wang, Xiao-Jin Wang, Lai Wei, Qing Xie, Wen Xie, Chang-Qing Yang, Dong-Liang Yang, Yan-Yan Yu, Min-de Zeng, Li Zhang, Xin-Yan Zhao, Hui Zhuang
Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells...
April 12, 2017: Hepatology International
https://www.readbyqxmd.com/read/28398242/drug-induced-liver-injury-can-biomarkers-assist-rucam-in-causality-assessment
#11
REVIEW
Rolf Teschke, Johannes Schulze, Axel Eickhoff, Gaby Danan
Drug induced liver injury (DILI) is a potentially serious adverse reaction in a few susceptible individuals under therapy by various drugs. Health care professionals facing DILI are confronted with a wealth of drug-unrelated liver diseases with high incidence and prevalence rates, which can confound the DILI diagnosis. Searching for alternative causes is a key element of RUCAM (Roussel Uclaf Causality Assessment Method) to assess rigorously causality in suspected DILI cases. Diagnostic biomarkers as blood tests would be a great help to clinicians, regulators, and pharmaceutical industry would be more comfortable if, in addition to RUCAM, causality of DILI can be confirmed...
April 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28391356/rat-precision-cut-liver-slices-predict-drug-induced-cholestatic-injury
#12
Viktoriia Starokozhko, Rick Greupink, Petra van de Broek, Nashwa Soliman, Samiksha Ghimire, Inge A M de Graaf, Geny M M Groothuis
Drug-induced cholestasis (DIC) is one of the leading manifestations of drug-induced liver injury (DILI). As the underlying mechanisms for DIC are not fully known and specific and predictive biomarkers and pre-clinical models are lacking, the occurrence of DIC is often only reported when the drug has been approved for registration. Therefore, appropriate models that predict the cholestatic potential of drug candidates and/or provide insight into the mechanism of DIC are highly needed. We investigated the application of rat precision-cut liver slices (PCLS) to predict DIC, using several biomarkers of cholestasis: hepatocyte viability, intracellular accumulation of total as well as individual bile acids and changes in the expression of genes known to play a role in cholestasis...
April 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28388864/clinical-and-histologic-features-of-azathioprine-induced-hepatotoxicity
#13
Sith Siramolpiwat, Dussadee Sakonlaya
BACKGROUND: Hepatoxicity is a relative uncommon complication related with Azathioprine, however most studies were performed in inflammatory bowel diseases patients. The aim of this study is to report the clinical profile of patients with Azathioprine-induced hepatotoxicity. METHODS: All medical records of patients received Azathioprine from 2010 to 2015 were retrospectively reviewed. Hepatotoxicity was defined as serum alanine aminotransferase (ALT) or aspatate aminotransferase (AST) or total bilirubin >2 times upper limit normal...
April 7, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28388498/raman-spectroscopy-for-the-detection-of-organ-distribution-and-clearance-of-pegylated-reduced-graphene-oxide-and-biological-consequences
#14
Santhakumar Syama, Willi Paul, Arumugam Sabareeswaran, Parayanthala Valappil Mohanan
Graphene, a 2D carbon material has found vast application in biomedical field because of its exciting physico-chemical properties. The large planar sheet like structure helps graphene to act as an effective carrier of drug or biomolecules in enormous amount. However, limited data available on the biocompatibility of graphene upon interaction with the biological system prompts us to evaluate their toxicity in animal model. In this study organ distribution, clearance and toxicity of PEGylated reduced nanographene (PrGO) on Swiss Albino mice was investigated after intraperitoneal and intravenous administration...
March 28, 2017: Biomaterials
https://www.readbyqxmd.com/read/28387740/protective-effect-of-bicyclol-on-anti-tuberculosis-drug-induced-liver-injury-in-rats
#15
Xin Liu, Manman Zhao, Jiaqi Mi, Hui Chen, Li Sheng, Yan Li
The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB) drug-induced liver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral administration of an anti-TB drug once a day for 30 days. Liver injury was evaluated by biochemical and histopathological examinations. Lipid peroxidation, mitochondrial function, and the activity of antioxidants were measured by spectrophotometric methods...
April 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28386997/the-transformation-in-biomarker-detection-and-management-of-drug-induced-liver-injury
#16
REVIEW
Rachel J Church, Paul B Watkins
Drug-induced liver injury (DILI) is a major concern for patients, care givers and the pharmaceutical industry. Interpretation of the serum biomarkers routinely used to detect and monitor DILI, which have not changed in almost 50 years, can be improved with recently proposed models employing quantitative systems pharmacology. In addition, several newer serum biomarkers are showing great promise. Studies in rodents indicate that the ratio of the caspase cleaved fragment of cytokeratin 18 to total K18 in serum (termed the "apoptotic index") estimates the relative proportions of apoptosis vs necrosis during drug-induced liver injury...
April 7, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28385542/model-systems-for-studying-the-role-of-canalicular-efflux-transporters-in-drug-induced-cholestatic-liver-disease
#17
REVIEW
Bruno Stieger, Zainab M Mahdi
Bile formation is a key function of the liver. Disturbance of bile flow may lead to liver disease and is called cholestasis. Cholestasis may be inherited such as for example in progressive familial intrahepatic cholestasis or acquired, such as for example by drug-mediated inhibition of bile salt export from hepatocytes into the canaliculi. The key transport system for exporting bile salts into the canaliculi is the bile salt export pump. Inhibition of the bile salt export pump by drugs is a well-established cause of drug-induced cholestasis...
April 3, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28383671/drug-induced-liver-injury-in-oncology
#18
A D Ricart
Liver regeneration has been an adaptation of vertebrates through evolutionary events to protect them from environmental pressures (e.g. ingested toxins). Elevated serum levels of aminotransferases generally indicate liver injury, but do not necessarily reflect or predict hepatotoxicity. Drug-induced liver injury (DILI) is first classified as predictable or unpredictable (idiosyncratic). Predictable DILI is dose-related and occurs shortly after exposure (e.g. high dose alkylating agents). Unpredictable reactions result from a succession of unlikely events, a "multihit" process (e...
April 5, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28380448/glibenclamide-a-diabetic-drug-prevents-acute-radiationinduced-liver-injury-of-mice-via-up-regulating-intracellular-ros-and-subsequently-activating-akt-nf-%C3%AE%C2%BAb-pathway
#19
Hu Liu, Shichao Wang, Zhao Wu, Ziyun Huang, Wei You Chen, Yanyong Yang, Jianguo Cui, Cong Liu, Hainan Zhao, Jiaming Guo, Pei Zhang, Fu Gao, Bailong Li, Jianming Cai
BACKGROUND: Acute radiation-induced liver injury is a limitation for hepatoma radiotherapy. Come so far the clinical treatments are insufficient. The effective, specific, low toxicity and novel drugs are in powerful need. Glibenclamide is a common hypoglycemic. Some studies have revealed its relation with intracellular reactive oxygen species, the crucial mediator to radiation injury. This study is aimed to investigate if glibenclamide could act on the acute radiation-induced liver injury...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28379596/liver-transplantation-for-drug-induced-acute-liver-failure
#20
M Biolato, C Araneo, G Marrone, A Liguori, L Miele, F R Ponziani, A Gasbarrini, A Grieco
OBJECTIVES: To summarize the different clinical features of drug-induced acute liver failure, the diagnostic work-up, conservative management and the prognostic scores currently used to list patients for liver transplantation. EVIDENCE AND INFORMATION SOURCES: The current review is based on an analysis of the current literature and the caseload experience of the Authors on this topic. STATE OF THE ART: Drug-induced liver injury is the leading cause of acute liver failure in the adult population in Western countries, with a transplant-free survival rate of less than 50%...
March 2017: European Review for Medical and Pharmacological Sciences
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