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Hepatotoxicity

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https://www.readbyqxmd.com/read/29793165/inhibition-of-acetaminophen-induced-hepatotoxicity-in-mice-by-exogenous-thymosin%C3%AE-4-treatment
#1
Lei Wang, Xiankui Li, Cai Chen
OBJECTIVE: To study the effects of exogenous thymosinβ4 (Tβ4) treatment in acetaminophen (APAP)-induced hepatotoxicity. METHODS: Liver injury was induced in mice by a single intraperitoneal injection of APAP (500 mg/kg). Exogenous Tβ4 was intraperitoneally administrated at 0 h, 2 h and 4 h after APAP injection. Chloroquine (CQ) (60 mg/kg) was intraperitoneally injected 2 h before APAP administration to inhibit autophagy. Six hours after APAP injection liver injury was evaluated by histological examinations, biochemical measurements and enzyme linked immunosorbent assay (ELISAs)...
May 21, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29792719/-sinusoidal-obstruction-syndrome-induced-by-monocrotaline-in-a-large-animal-experiment-a-pilot-study
#2
R Pálek, V Liška, V Třeška, J Rosendorf, M Emingr, V Tégl, A Králíčková, K Bajcurová, M Jiřík, Z Tonar
INTRODUCTION: Sinusoidal obstruction syndrome (SOS) is a disease which is caused by toxic injury to hepatic sinusoids. This syndrome is most frequently caused by myeloablative radiochemotherapy in patients before hematopoietic stem cells transplantation and also by oxaliplatin mainly in patients with colorectal liver metastases. The aim of this study was to establish a large animal model of SOS, which would enable further study of this disease and facilitate translation of experimental outcomes into human medicine...
2018: Rozhledy V Chirurgii: Měsíčník Československé Chirurgické Společnosti
https://www.readbyqxmd.com/read/29792347/fewer-adverse-effects-associated-with-a-modified-two-bag-intravenous-acetylcysteine-protocol-compared-to-traditional-three-bag-regimen-in-paracetamol-overdose
#3
Lars E Schmidt, Ditlev N Rasmussen, Tonny S Petersen, Ines M Macias-Perez, Leo Pavliv, Byron Kaelin, Richard C Dart, Kim Dalhoff
CONTEXT: The intravenous (IV) N-acetylcysteine (NAC) regimen used worldwide in paracetamol overdose is complex with three separate weight-based doses and is associated with a high incidence of adverse events including non-allergic anaphylactoid reactions (NAARs). In 2012, Denmark adopted the two-bag IV NAC regimen which combined the first two infusions of the three-bag regimen and kept the third infusion unchanged. We compared the safety and efficacy of the two-bag IV NAC regimen with the traditional Danish three-bag regimen...
May 24, 2018: Clinical Toxicology
https://www.readbyqxmd.com/read/29791258/licorice-root-extract-and-magnesium-isoglycyrrhizinate-protect-against-triptolide-induced-hepatotoxicity-via-up-regulation-of-the-nrf2-pathway
#4
Qin-You Tan, Qian Hu, Sheng-Nan Zhu, Lu-Lu Jia, Juan Xiao, Hua-Zhen Su, Shao-Yuan Huang, Jing Zhang, Junfei Jin
Triptolide, the predominant biologically active component of the Chinese herb Tripterygium wilfordii Hook f., possesses numerous pharmacological activities, including anti-inflammatory, anti-fertility, anti-neoplastic, and immunosuppressive effects. However, toxicity and severe adverse effects, particularly hepatotoxicity, limit the clinical application of triptolide. Licorice root extract contains various bioactive compounds and is potent hepatoprotective. Magnesium isoglycyrrhizinate, a magnesium salt of the 18α-glycyrrhizic acid stereoisomer of glycyrrhizic acid, is used clinically in China to treat chronic viral hepatitis and acute drug-induced liver injury...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29791174/-drug-and-herbal-hepatotoxicity-an-overview-of-clinical-classifications
#5
Mária Szántová, Jozef Sedlačko, Martina Jakabovičová
Drug induced liver injury (DILI) is often underdiagnosed disease with increasing incidence. In developed countries it belongs to the leading causes of acute liver failure. Risk groups are women and persons older than 60 years. The work summarizes the up to date information on diagnosis and mostly used classifications on DILI. It is quite often and serious complication of medicament therapy. DILI belongs to the most often cause of acute hepatic failure in the old age in developed countries. Diagnostic procedure includes medical history (time correlation with drug intake), clinical symptoms and blood tests...
2018: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29790616/in-vitro-and-in-vivo-metabolic-profiles-of-fasiglifam-by-using-ultra-high-performance-liquid-chromatography-combined-with-q-exactive-orbitrap-tandem-mass-spectrometry
#6
Jin-Qi Li, Jia-Feng Wang, Jie Li, Shu-Han Zhang, Dan He, Rong-Sheng Tong, Shu-Ya She
RATIONALE: Fasiglifam is an orally available and selective partial agonist of hGPR40 receptor, which was unexpectedly terminated at phase III clinical trials due to its severe hepatotoxicity. To fully understand its mechanism of action, it is necessary to investigate the in vitro and in vivo metabolic profiles of fasiglifam. METHODS: For in vitro metabolism, fasiglifam was incubated with rat or human liver microsomes in the presence of NADPH, GSH and UDPGA for 60 min...
May 23, 2018: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/29790527/protective-activity-of-tovophyllin-a-a-xanthone-isolated-from-garcinia-mangostana-pericarps-against-acetaminophen-induced-liver-damage-role-of-nrf2-activation
#7
Sabrin R M Ibrahim, Dina S El-Agamy, Hossam M Abdallah, Nishat Ahmed, Mohamed A Elkablawy, Gamal A Mohamed
Garcinia mangostana L. (GM, family Guttiferae) is one of the most widely recognized tropical fruits. GM is a wealthy pool of xanthones that exhibit a wide range of bioactivities. Tovophyllin A (TA) separated from GM pericarps was tested for its efficacy to ameliorate acetaminophen (APAP)-induced liver injury. Mice were injected with a single dose of APAP with or without TA pretreatment. The protective effects of TA against APAP-induced liver damage were evident through amelioration of serum indices of hepatotoxicity and improvement of hepatic histopathologic lesions...
May 23, 2018: Food & Function
https://www.readbyqxmd.com/read/29788510/predicting-drug-induced-liver-injury-using-ensemble-learning-methods-and-molecular-fingerprints
#8
Haixin Ai, Wen Chen, Li Zhang, Liangchao Huang, Zimo Yin, Huan Hu, Qi Zhao, Jian Zhao, Hongsheng Liu
Drug-induced liver injury (DILI) is a major safety concern in the drug-development process, and various methods have been proposed to predict the hepatotoxicity of compounds during the early stages of drug trials. In this study, we developed an ensemble model using three machine learning algorithms and 12 molecular fingerprints from a dataset containing 1,241 diverse compounds. The ensemble model achieved an average accuracy of 71.1±2.6%, sensitivity of 79.9±3.6%, specificity of 60.3±4.8%, and area under the receiver operating characteristic curve (AUC) of 0...
May 21, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29787320/gemtuzumab-ozogamicin-for-the-treatment-of-acute-myeloid-leukemia
#9
Jeffrey Baron, Eunice S Wang
Gemtuzumab ozogamicin (GO) is an antibody-drug conjugate consisting of a monoclonal antibody targeting CD33 linked to a cytotoxic derivative of calicheamicin. Despite the known clinical efficacy in relapsed/refractory acute myeloid leukemia (AML), GO was withdrawn from the market in 2010 due to increased early deaths seen in newly diagnosed AML patients receiving GO + intensive chemotherapy. In 2017, new data on the clinical efficacy and safety of GO administered on a fractionated dosing schedule led to re-approval for newly diagnosed and relapsed/refractory AML...
May 22, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29786555/innate-immunity-in-stem-cell-derived-hepatocytes
#10
REVIEW
Lena Fischer, David C Hay, Cliona O'Farrelly
Stem cell-derived hepatocyte-like cells (HLCs) offer great opportunities for studies of host-pathogen interactions and tissue regeneration, as well as hepatotoxicity. To reliably predict the outcome of infection or to enhance graft survival, a finely tuned innate immune system is essential. Hepatocytes have long been considered solely metabolic and their critical innate immune potential is only recently gaining attention. Viral infection studies show that pathogen detection by cytosolic receptors leads to interferon (IFN) induction in primary hepatocytes and HLCs...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29785108/the-protective-role-of-quercetin-and-arginine-on-gold-nanoparticles-induced-hepatotoxicity-in-rats
#11
Mohamed Anwar K Abdelhalim, Sherif A Abdelmottaleb Moussa, Huda Abdo Yahya Qaid
Background: The aim of the study was to confirm the hepatotoxicity induced by small-sized gold nanoparticles (GNPs) and evaluate the role of quercetin (Qur) and arginine (Arg) against hepatotoxicity caused by GNPs. Methods: Twenty-five healthy male Wistar-Kyoto rats were used. GNPs were administered intraperitoneally to these rats at the dose of 50 μL for seven consecutive days. The role of Qur and Arg antioxidants against toxicity induced by GNPs was detected through the measurement of serum liver function and oxidative stress biomarkers in the liver tissues...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29784840/oxidative-stress-and-first-line-antituberculosis-drug-induced-hepatotoxicity
#12
Wing Wai Yew, Kwok Chiu Chang, Denise P Chan
Hepatotoxicity induced by antituberculosis drugs is a serious adverse reaction with significant morbidity and even rarely mortality. This form of toxicity potentially impacts the treatment outcome of tuberculosis in some patients. Confining to first-line antituberculosis drugs, this review addresses whether and how oxidative stress, and more broadly, disturbance in redox homeostasis alongside mitochondrial dysfunction, may contribute to the hepatotoxicity induced by them. Risk factors for such toxicity that have been identified, in addition to genetic factors, principally include old age, malnutrition, alcoholism, chronic hepatitis C and chronic hepatitis B infection, HIV infection and pre-existing liver disease...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29783990/severe-hepatopathy-and-neurological-deterioration-after-start-of-valproate-treatment-in-a-6-year-old-child-with-mitochondrial-tryptophanyl-trna-synthetase-deficiency
#13
Elise Vantroys, Joél Smet, Arnaud V Vanlander, Sarah Vergult, Ruth De Bruyne, Frank Roels, Hedwig Stepman, Herbert Roeyers, Björn Menten, Rudy Van Coster
BACKGROUND: The first subjects with deficiency of mitochondrial tryptophanyl-tRNA synthetase (WARS2) were reported in 2017. Their clinical characteristics can be subdivided into three phenotypes (neonatal phenotype, severe infantile onset phenotype, Parkinson-like phenotype). RESULTS: Here, we report on a subject who presented with early developmental delay, motor weakness and intellectual disability and who was considered during several years as having a non-progressive encephalopathy...
May 21, 2018: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/29783726/case-report-of-isoniazid-related-acute-liver-failure-requiring-liver-transplantation
#14
Andrew A Li, Pratima Dibba, George Cholankeril, Donghee Kim, Aijaz Ahmed
The prevalence of latent tuberculosis infection (LTBI) in the United States in 2011 and 2012 was estimated at 4.4⁻4.8%. As of 2015, 12.4 million people still possessed LTBI. Isoniazid, or isonicotinic acid hydrazine (INH), is the most commonly used medication among varying regimens that exist in the treatment of tuberculosis and LTBI. INH-related hepatotoxicity is a well-known adverse effect of its use, often causing asymptomatic elevations in serum aminotransferase levels. These elevations are typically transient and reversible, but can cause acute, clinically-significant liver injury in rare cases...
May 19, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29782917/detoxification-and-immunoprotection-of-zn-ii-curcumin-in-juvenile-pacific-white-shrimp-litopenaeus-vannamei-feed-with-aflatoxin-b1
#15
Ying-Ying Yu, Jin Niu, Pen Yin, Yong-Jian Liu, Li-Xia Tian, Donghui Xu
Aflatoxins, which was produced by Aspergillus flavus or Aspergillus parasiticus fungi during grain and feed processing or storage, could cause severe health problems and reduction of yield during shrimp cultures. To evaluate toxic effects of aflatoxin B1 (AFB1) in juvenile Pacific white shrimp (Litopenaeus vannamei) and potential protective effect of Zn(II)-curcumin (Zn-CM), four experimental diets (control, 500 μg/kg AFB1, 500 μg/kg AFB1+100 mg/kg Zn-CM, 500 μg/kg AFB1+200 mg/kg Zn-CM) were formulated in quadruplicate to feed the shrimp for 8 weeks...
May 18, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29778019/phoenix-dactylifera-protects-against-oxidative-stress-and-hepatic-injury-induced-by-paracetamol-intoxication-in-rats
#16
Gamal A Salem, Ahmed Shaban, Hussain A Diab, Wesam A Elsaghayer, Manal D Mjedib, Aomassad M Hnesh, Ravi P Sahu
The current studies were sought to determine effects of antioxidant potential of aqueous and methanolic extracts of Phoenix dactylifera leaves (PLAE and PLME) against the widely-used analgesic paracetamol (PCM) induced hepatotoxicity. Groups of rats were treated with or without PCM (1500 mg/kg), PLAE and PLME (300 mg/kg) and n-acetylcysteine (NAC, 50 mg/kg) followed by assessments of liver function tests, oxidative stress, antioxidant defenses, and hepatotoxicity. We observed that PCM significantly elevated serum liver markers, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and bilirubin compared to control (untreated) group...
May 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29777724/novel-mirna-biomarkers-for-genotoxicity-screening-in-mouse
#17
Hiroyuki Oka, Koichi Masuno, Takeki Uehara, Toru Okamoto, Yoshiharu Matsuura, Toru Nakano, Shinpei Yamaguchi
The genotoxic potential of drugs is a serious problem, and its evaluation is one of the most critical processes of drug development. Although the comet assay of compound-exposed tissue is a frequently used genotoxicity test, its high false-positive rate is a major complication, and we consistently obtained false-positive results using the comet assay of mouse liver for nine hepatotoxic non-genotoxins (NGTXs). To identify novel genotoxin (GTX)-specific biomarkers, we screened the expression of 750 microRNAs (miRNAs) in the livers of mice treated with GTXs or NGTXs...
May 16, 2018: Toxicology
https://www.readbyqxmd.com/read/29776838/hot-aqueous-leaf-extract-of-lasianthera-africana-icacinaceae-attenuates-rifampicin-isoniazid-induced-hepatotoxicity
#18
Lucky Legbosi Nwidu, Raphael Ellis Teme
OBJECTIVES: The aim of this study is to evaluate the hepatoprotective effect of Lasianthera africana (Icacinaceae) against isoniazid (INH) and rifampicin (RIF)-induced liver damage in rats. METHODS: The hepatoprotective effects of hot aqueous L. africana (HALA) leaf extract (0.1-1 g/kg) and silymarin (50 mg/kg) were assessed in a model of oxidative liver damage induced by RIF and INH (100 mg/kg each) in Wistar rats for 28 days. Biochemical markers of hepatic damage such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were assessed...
May 8, 2018: Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29774767/the-role-of-hepatic-antioxidant-capacity-and-hepatobiliary-transporter-in-liver-injury-induced-by-isopsoralen-in-zebrafish-larvae
#19
Y Zhang, Y Zhang, J Li, Y Chen, L Han, Q He, J Chu, K Liu
Isopsoralen is the main component of the Chinese medicine psoralen, which has antitumour activity and can be used for the treatment of osteoporosis. However, the mechanism behind its hepatotoxicity has not yet been elucidated. In this study, the hepatotoxicity of isopsoralen was investigated using zebrafish. Isopsoralen treatment groups of 25, 50 and 100 μM were established. The mortality, liver morphology changes, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver histopathology and mRNA levels of liver injury-related genes in zebrafish larvae were measured...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29774103/bevacizumab-exacerbates-sinusoidal-obstruction-syndrome-sos-in-the-animal-model-and-increases-mmp-9-production
#20
Azin Jafari, Hanno Matthaei, Sven Wehner, Tolga Tonguc, Jörg C Kalff, Steffen Manekeller
Background: Thanks to modern multimodal treatment the ouctome of patients with colorectal cancer has experienced significant improvements. As a downside, agent specific side effects have been observed such as sinusoidal obstruction syndrome (SOS) after oxaliplatin chemotherapy (OX). Bevazicumab targeting VEGF is nowadays comprehensively used in combination protocols with OX but its impact on hepatotoxicity is thus far elusive and focus of the present study. Results: After MCT administration 67% of animals developed SOS...
April 24, 2018: Oncotarget
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