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https://www.readbyqxmd.com/read/28645575/prediction-of-drug-induced-immune-mediated-hepatotoxicity-using-hepatocyte-like-cells-derived-from-human-embryonic-stem-cells
#1
Dong Eon Kim, Mi-Jin Jang, Young Ran Kim, Joo-Young Lee, Eun Byul Cho, Eunha Kim, Yeji Kim, Mi Young Kim, Won-Il Jeong, Seyun Kim, Yong-Mahn Han, Seung-Hyo Lee
Drug-induced liver injury (DILI) is a leading cause of liver disease and a key safety factor during drug development. In addition to the initiation events of drug-specific hepatotoxicity, dysregulated immune responses have been proposed as major pathological events of DILI. Thus, there is a need for a reliable cell culture model with which to assess drug-induced immune reactions to predict hepatotoxicity for drug development. To this end, stem cell-derived hepatocytes have shown great potentials. Here we report that hepatocyte-like cells derived from human embryonic stem cells (hES-HLCs) can be used to evaluate drug-induced hepatotoxic immunological events...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28636309/quantitative-chemical-proteomic-profiling-of-the-in-vivo-targets-of-reactive-drug-metabolites
#2
Landon R Whitby, R Scott Obach, Gabriel M Simon, Matthew M Hayward, Benjamin F Cravatt
Idiosyncratic liver toxicity represents an important problem in drug research and pharmacotherapy. Reactive drug metabolites that modify proteins are thought to be a principal factor in drug-induced liver injury. Here, we describe a quantitative chemical proteomic method to identify the targets of reactive drug metabolites in vivo. Treating mice with clickable analogues of four representative hepatotoxic drugs, we demonstrate extensive covalent binding that is confined primarily to the liver. Each drug exhibited a distinct target profile that, in certain cases, showed strong enrichment for specific metabolic pathways (e...
June 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28630953/distribution-of-acetylated-histone-4-in-normal-liver-and-acetaminophen-induced-liver-damage
#3
N Nakamura, Chang C-W, X Yang, Q Shi, W F Salminen, A Suzuki
To describe cell-specific acetylation of histones and their zonal localization in normal mouse liver and characterize their changes in acetaminophen (APAP)-damaged mouse liver 24 hr after APAP exposure, we performed an immunohistochemical study using normal and APAP-injured mouse livers. Cell-specific expression of acetylated H4 was observed in normal mouse liver. The highest acetylated H4 expression levels were found in bile duct epithelial cells, followed by sinusoidal non-parenchymal cells, venous endothelial cells, and hepatocytes...
2017: SM J Biol
https://www.readbyqxmd.com/read/28627888/investigation-of-drug-induced-hepatotoxicity-and-its-remediation-pathway-with-reaction-based-fluorescent-probes
#4
Dan Cheng, Wang Xu, Lin Yuan, Xiao-Bing Zhang
Drug-induced liver injury (DILI) is considered a serious problem related to public health, due to its unpredictability and acute response. The level of peroxynitrite (ONOO-) generated in liver has long been regarded as a biomarker for the prediction and measurement of DILI. Herein we present two reaction based fluorescent probes (Naph-ONOO- and Rhod-ONOO-) for ONOO- through a novel and universally applicable mechanism: ONOO- mediated deprotection of -keto caged fluorophores. Among them, Rhod-ONOO- can selectively accumulate and react in mitochondria, one of the main sources of ONOO-, with a substantial lower nano-molar sensitivity of 43 nM...
June 19, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28626497/hepatoprotective-effect-of-polyphenol-enriched-fraction-from-folium-microcos-on-oxidative-stress-and-apoptosis-in-acetaminophen-induced-liver-injury-in-mice
#5
Hongtan Wu, Gang Zhang, Lisen Huang, Haiyue Pang, Na Zhang, Yupei Chen, Gueyhorng Wang
Folium Microcos (FM), the leaves of Microcos paniculata L., shows various biological functions including antioxidant activity and α-glucosidase inhibitory effect. However, its therapeutic potential in acute liver injury is still unknown. This study investigated the hepatoprotective effect and underlying mechanisms of the polyphenol-enriched fraction (FMF) from Folium Microcos. FMF exhibited strong free radical scavenging activities and prevented HepG2/Hepa1-6 cells from hydrogen peroxide- (H2O2-) induced ROS production and apoptosis in vitro...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28624597/suppressive-effect-of-kamebakaurin-on-acetaminophen-induced-hepatotoxicity-by-inhibiting-lipid-peroxidation-and-inflammatory-response-in-mice
#6
Hiroki Yoshioka, Yutaka Aoyagi, Nobuyuki Fukuishi, Ming-Yu Gui, Yong-Ri Jin, Xu-Wen Li, Yoshiyuki Adachi, Naohito Ohno, Koichi Takeya, Yukio Hitotsuyanagi, Nobuhiko Miura, Tsunemasa Nonogaki
BACKGROUND: Kamebakaurin (KA) is an ent-kaurane diterpenoid known to have anti-inflammatory potential. In the current study, we investigated whether pretreatment with KA could ameliorate acetaminophen (APAP)-induced hepatotoxicity by inhibiting the anti-inflammatory response in mice. METHODS: Seven-week-old C57BL/6J mice were orally administered KA or olive oil emulsion for seven days. Twenty-four hours after the last KA or olive oil administration, the mice were intraperitoneally injected with 400mg/kg APAP or saline under feed deprived condition...
April 12, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28620383/ly6c-hi-monocytes-and-their-macrophage-descendants-regulate-neutrophil-function-and-clearance-in-acetaminophen-induced-liver-injury
#7
Nadine Graubardt, Milena Vugman, Odelia Mouhadeb, Gabriele Caliari, Metsada Pasmanik-Chor, Debby Reuveni, Ehud Zigmond, Eli Brazowski, Eyal David, Lousie Chappell-Maor, Steffen Jung, Chen Varol
Monocyte-derived macrophages (MoMF) play a pivotal role in the resolution of acetaminophen-induced liver injury (AILI). Timely termination of neutrophil activity and their clearance are essential for liver regeneration following injury. Here, we show that infiltrating Ly6C(hi) monocytes, their macrophage descendants, and neutrophils spatially and temporally overlap in the centrilobular necrotic areas during the necroinflammatory and resolution phases of AILI. At the necroinflammatory phase, inducible ablation of circulating Ly6C(hi) monocytes resulted in reduced numbers and fractions of reactive oxygen species (ROS)-producing neutrophils...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28616908/-the-correlation-between-micrornas-in-serum-and-the-extent-of-liver-injury
#8
Yi-Nan Zuo, Xue-Ling He, Xue-Ni Shi, Shi-Hang Wei, Hai-Lin Yin
OBJECTIVES: To investigate the correlation between the absolute quantification of the microRNAs (miR-122, miR-451, miR-92a, miR-192) in serum during acute liver injury and the extent of liver injury on rat models of CCl4 induced acute liver injury and mice models of acetaminophen (APAP) induced acute liver injury. Furthermore, to investigate the correlation between the absolute quantification of microRNAs in serum and the drug induced liver injury pathological scoring system (DILI-PSS)...
May 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28612711/alleviative-effects-from-boswellic-acid-on-acetaminophen-induced-hepatic-injury-corrected-and-republished-from-biomedicine-taipei-2016-jun-6-2-9-doi-10-7603-s40681-016-0009-1pmcid-pmc4864770
#9
Lung-Che Chen, Li-Hong Hu, Mei-Chin Yin
Protective effects of boswellic acid (BA) against acetaminophen (APAP)-induced hepatotoxicity in Balb/ cA mice were examined. BA, at 0.05 or 0.1%, was supplied for 4 weeks. Acute liver injury was induced by APAP treatment. Results showed that BA intake increased hepatic BA bioavailability. APAP treatment decreased glutathione (GSH) level, increased reactive oxygen species (ROS) and oxidized glutathione (GSSG) production; and lowered activity and protein expression of glutathione reductase (GR) and heme oxygenase (HO)-1 in liver...
June 2017: BioMedicine
https://www.readbyqxmd.com/read/28611340/role-of-n-acetylcysteine-treatment-in-non-acetaminophen-induced-acute-liver-failure-a-prospective-study
#10
Tauseef Nabi, Sumaiya Nabi, Nadeema Rafiq, Altaf Shah
BACKGROUND/AIMS: Acute liver failure (ALF) is a rare but severe medical emergency. To date, there is no established treatment for non-acetaminophen-induced acute liver failure (NAI-ALF) other than liver transplantation, and little is known about the use of N-acetylcysteine (NAC) in NAI-ALF. A randomized case control study was conducted with the aim to determine the effect of NAC on the mortality of NAI-ALF patients, as well as to evaluate the safety and efficacy of NAC use. PATIENTS AND METHODS: A total of 80 patients diagnosed with NAI-ALF were included in the study...
May 2017: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/28611335/the-role-of-n-acetylcysteine-in-the-treatment-of-non-acetaminophen-acute-liver-failure
#11
EDITORIAL
Anouar Teriaky
No abstract text is available yet for this article.
May 2017: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/28609563/bayesian-forecasting-tool-to-predict-the-need-for-antidote-in-acute-acetaminophen-overdose
#12
Julie Desrochers, Jessica Wojciechowski, Wendy Klein-Schwartz, Jogarao V S Gobburu, Mathangi Gopalakrishnan
STUDY OBJECTIVE: Acetaminophen (APAP) overdose is the leading cause of acute liver injury in the United States. Patients with elevated plasma acetaminophen concentrations (PAC) require hepatoprotective treatment with N-acetylcysteine (NAC). These patients have been primarily risk-stratified using the Rumack-Matthew nomogram. Previous studies of acute APAP overdoses found that the nomogram failed to accurately predict the need for the antidote. The objectives of this study were to develop a population pharmacokinetic (PK) model for APAP following acute overdose and evaluate the utility of population PK model-based Bayesian forecasting in NAC administration decisions...
June 13, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28603092/crosstalk-of-liver-immune-cells-and-cell-death-mechanisms-in-different-murine-models-of-liver-injury-and-its-clinical-relevance
#13
Hilal Ahmad Khan, Muhammad Zishan Ahmad, Junaid Ali Khan, Muhammad Imran Arshad
BACKGROUND: Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions...
June 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/28594770/placental-abruption-with-delayed-fetal-compromise-in-maternal-acetaminophen-toxicity
#14
Juliana Taney, Hannah Anastasio, Amanda Paternostro, Vincenzo Berghella, Amanda Roman
BACKGROUND: After maternal acetaminophen overdose, fetal fulminant liver failure, stillbirth, neonatal death, or preterm delivery may occur. CASE: A 27-year-old woman, gravida 2 para 1, presented at 28 weeks of gestation after unintentional acetaminophen overdose. Four days after ingestion, her laboratory values worsened, including serum aspartate aminotransferase of 5,460 units/L, alanine aminotransferase of 4,936 units/L, and international normalized ratio of 2...
June 6, 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28591702/fgf21-functions-as-a-sensitive-biomarker-of-apap-treated-patients-and-mice
#15
Rong Li, Chao Guo, Xinmou Wu, Zhaoquan Huang, Jian Chen
Acetaminophen (APAP) is a common medication that induces hepatocellular damage in a time- or dose-dependent manner. Fibroblast growth factor 21 (FGF21) exerts a series of biological effects, including cellular repair. Compared to clinical diagnosis parameters, we aimed to evaluate whether FGF21 can serve as a sensitive biomarker for APAP-induced liver impairment. In the present study, we discussed comparable data from APAP-treated patients and parallelly established APAP-exposed mice for investigation. The resulting human serological data showed that APAP-treated patients have a visible reduction of FGF21 expression in undetected liver impairment of clinical diagnosis...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28583670/hepatic-hypoxia-inducible-factors-inhibit-ppar%C3%AE-expression-to-exacerbate-acetaminophen-induced-oxidative-stress-and-hepatotoxicity
#16
Dawei Li, Yingdong Du, Xiaodong Yuan, Xiaoxiao Han, Zhen Dong, Xiaosong Chen, Haoyu Wu, Jianjun Zhang, Longmei Xu, Conghui Han, Ming Zhang, Qiang Xia
Oxidative stress has a critical role in the pathogenesis of acetaminophen (APAP) induced hepatocellular necrosis, and the identification of novel approaches to attenuate oxidative stress is essential to prevent/revert the disease. This study investigated the role of both HIF-1 and HIF-2 in the pathogenesis of APAP-induced oxidative stress, as well as the underlying mechanisms. In the present study, we initially found that knockout of HIF-1α or HIF-2α reduced APAP toxicity, and double knockout afforded the best protection...
June 3, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28580117/two-photon-fluorescent-probe-for-revealing-drug-induced-hepatotoxicity-via-mapping-fluctuation-of-peroxynitrite
#17
Yong Li, Xilei Xie, Xiu'e Yang, Mengmeng Li, Xiaoyun Jiao, Yuhui Sun, Xu Wang, Bo Tang
Drug-induced injury has attracted increasing attention in public health issues. Among them, hepatotoxicity has been regarded as the leading clinical problem caused by drug toxicity. However, owing to the complexity of the involved pathophysiological mechanisms and the lack of noninvasive, straightforward, and real-time tools, drug-induced hepatotoxicity has rarely been predicted satisfactorily. In this paper, by utilizing the reactive species peroxynitrite (ONOO(-)) as a biomarker, we present a two-photon fluorescent probe, TP-KA, holding rapid response, high specificity and sensitivity towards ONOO(-), to investigate drug (acetaminophen and tolcapone)-related liver injury and the remediate effect of N-acetyl cysteine (NAC)...
May 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28579595/study-on-the-increased-probability-of-detecting-adverse-drug-reactions-based-on-bayes-theorem-evaluation-of-the-usefulness-of-information-on-the-onset-timing-of-adverse-drug-reactions
#18
Shinji Oshima, Takako Enjuji, Akio Negishi, Hayato Akimoto, Kousuke Ohara, Mitsuyoshi Okita, Sachihiko Numajiri, Naoko Inoue, Shigeru Ohshima, Akira Terao, Daisuke Kobayashi
In order to avoid adverse drug reactions (ADRs), pharmacists are reconstructing ADR-related information based on various types of data gathered from patients, and then providing this information to patients. Among the data provided to patients is the time-to-onset of ADRs after starting the medication (i.e., ADR onset timing information). However, a quantitative evaluation of the effect of onset timing information offered by pharmacists on the probability of ADRs occurring in patients receiving this information has not been reported to date...
June 3, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28577513/synergistic-protective-effect-of-picrorhiza-with-honey-in-acetaminophen-induced-hepatic-injury
#19
Prashant Gupta, Alok Tripathi, Tripti Agrawal, Chandradeo Narayan, B M Singh, Mohan Kumar, Arvind Kumar
Rhizome of picrorhiza along with honey prevents hepatic damage and cure the acetaminophen (paracetamol) induced hepatotoxicity by modulating the activity of hepatic enzymes. Here, we studied the in vivo effects of Picrorhiza kurroa and honey on acetaminophen induced hepatotoxicity Balb/c mice model. Hepatic histopathological observations of acetaminophen fed (day-6) group showed more congestion, hemorrhage, necrosis, distorted hepatic architecture and nuclear inclusion. Such damages were recompensed to normal by picrorhiza or honey alone or both in combinations...
August 2016: Indian Journal of Experimental Biology
https://www.readbyqxmd.com/read/28573237/protective-effect-of-moringa-peregrina-leaves-extract-on-acetaminophen-induced-liver-toxicity-in-albino-rats
#20
Samy Abdelfatah Abdel Azim, Mohamed Taha Abdelrahem, Mostafa Mohamed Said, Alshaimaa Khattab
BACKGROUND: Acetaminophen is a common antipyretic drug but at overdose can cause severe hepatotoxicity that may further develop into liver failure and hepatic centrilobular necrosis in experimental animals and humans. This study was undertaken to assess the ameliorative role of Moringa peregrina leaves extract against acetaminophen toxicity in rats. MATERIALS AND METHODS: Induction of hepatotoxicity was done by chronic oral administration of acetaminophen (750 mg/kg bwt) for 4 weeks...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
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