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Hepatotoxicity

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https://www.readbyqxmd.com/read/28436314/metabolomic-approaches-in-the-discovery-of-potential-urinary-biomarkers-of-drug-induced-liver-injury-dili
#1
Ana Margarida Araújo, Márcia Carvalho, Félix Carvalho, Maria de Lourdes Bastos, Paula Guedes de Pinho
Drug-induced liver injury (DILI) is a major safety issue during drug development, as well as the most common cause for the withdrawal of drugs from the pharmaceutical market. The identification of DILI biomarkers is a labor-intensive area. Conventional biomarkers are not specific and often only appear at significant levels when liver damage is substantial. Therefore, new biomarkers for early identification of hepatotoxicity during the drug discovery process are needed, thus resulting in lower development costs and safer drugs...
April 24, 2017: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/28435131/repression-of-acetaminophen-induced-hepatotoxicity-by-a-combination-of-celastrol-and-brilliant-blue-g
#2
Heba A Abdelaziz, Mohamed E Shaker, Mohamed F Hamed, Nariman M Gameil
The sterile inflammatory response is an eminent contributor to acetaminophen (APAP)-hepatotoxicity in humans. Recent advances unraveled an axial role of the NLRP3-inflammasome in APAP-post injury inflammation. Nevertheless, the role of signaling events preceded the NLRP3-inflammasome activation, like the transcription factor NF-κB and the purinergic receptor P2×7, is still unclear and needs further elucidation. Here, we investigated the pharmacological inhibition of these upstream signaling molecules by celastrol and brilliant blue G (BBG) (separately or simultaneously) in APAP-hepatotoxicity in mice...
April 20, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28433749/novel-sulphur-containing-imatinib-metabolites-found-by-untargeted-lc-hrms-analysis
#3
Ivo Vrobel, David Friedecký, Edgar Faber, Lukáš Najdekr, Kateřina Mičová, Radana Karlíková, Tomáš Adam
Untargeted metabolite profiling using high-resolution mass spectrometry coupled with liquid chromatography (LC-HRMS), followed by data analysis with the Compound Discoverer 2.0™ software, was used to study the metabolism of imatinib in humans with chronic myeloid leukemia. Plasma samples from control (drug-free) and patient (treated with imatinib) groups were analyzed in full-scan mode and the unknown ions occurring only in the patient group were then, as potential imatinib metabolites, subjected to multi-stage fragmentation in order to elucidate their structure...
April 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28433638/metabolomic-analysis-for-combined-hepatotoxicity-of-chlorpyrifos-and-cadmium-in-rats
#4
Ming-Yuan Xu, Pan Wang, Ying-Jian Sun, Yi-Jun Wu
Pesticides and heavy metals are widespread environmental pollutants. Although the acute toxicity of organophosphorus pesticide chlorpyrifos (CPF) and toxic heavy metal cadmium (Cd) is well characterized, the combined toxicity of CPF and Cd, especially the hepatotoxicity of the two chemicals with long-term exposure at a low dose, remained unclear. In this study, we investigated the toxicity in the liver of rats upon subchronic exposure to CPF and Cd at environmentally relevant doses. Rats were given three different doses (1/135 LD50, 1/45 LD50 and 1/15 LD50) of CPF and Cd as well as their mixtures by oral gavage for 90 days...
April 19, 2017: Toxicology
https://www.readbyqxmd.com/read/28432936/the-immunosuppressive-characteristics-of-fb1-by-inhibition-of-maturation-and-function-of-bmdcs
#5
Yinhuan Li, Yanhong Fan, Bingbing Xia, Qiuping Xiao, Qingqing Wang, Weidong Sun, Haibin Zhang, Chenghua He
Fumonisin B1 (FB1) is one kind of mycotoxins that has the neurotoxicity, carcinogenicity, hepatotoxicity and immunotoxicity produced by the fungus Fusarium verticillioides, which commonly infects corn and other crops and is harmful to animal and human health upon consumption of FB1-contaminated feed or food. However, the mechanism of immunotoxicity, especially the immunosuppression induced by FB1 is still unclear. The most pivotal cells in the induction of immune responses are dendritic cells (DCs). In this study, we used murine bone marrow-derived dendritic cells (BMDCs) as a model system to elucidate the effect of FB1 on the function of BMDCs through biological methods...
April 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28432048/solithromycin-a-novel-ketolide-antibiotic
#6
Michael J Buege, Jack E Brown, Samuel L Aitken
PURPOSE: The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, clinical safety, and current regulatory status of solithromycin are reviewed. SUMMARY: Solithromycin is a novel ketolide antibiotic developed for the treatment of community-acquired bacterial pneumonia (CABP). Its pharmacologic, pharmacokinetic, and pharmacodynamic properties provide activity against a broad range of intracellular organisms, including retained activity against pathogens displaying various mechanisms of macrolide resistance...
April 21, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28431933/caspofungin-versus-micafungin-in-the-incidence-of-hepatotoxicity-in%C3%A2-patients-with-normal-to-moderate-liver-failure
#7
Yuichi Shibata, Mao Hagihara, Hideo Kato, Noriyo Kawasumi, Jun Hirai, Naoya Nishiyama, Nobuhiro Asai, Yusuke Koizumi, Yuka Yamagishi, Katsuhiko Matsuura, Hiroshige Mikamo
BACKGROUND: One of the major adverse events of caspofungin and micafungin is hepatotoxicity, however, there are few reports compared the incidence of hepatotoxicity between caspofungin and micafungin. Herein, the primary objective of this study was to compare the incidence of hepatotoxicity between caspofungin and micafungin treatments for patients with fungal or suspected fungal infection. METHODS: In total, 201 patients [caspofungin group: 66 patients; micafungin group: 135 patients] treated with echinocandins from April 2014 to November 2015 at Aichi Medical University Hospital...
April 18, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28430700/prescriber-compliance-with-liver-monitoring-guidelines-for-pazopanib-in-the-postapproval-setting-results-from-a-distributed-research-network
#8
Sumitra Shantakumar, Beth L Nordstrom, Susan A Hall, Luc Djousse, Myrthe P P van Herk-Sukel, Kathy H Fraeman, David R Gagnon, Karen Chagin, Jeanenne J Nelson
OBJECTIVES: Pazopanib received US Food and Drug Administration approval in 2009 for advanced renal cell carcinoma. During clinical development, liver chemistry abnormalities and adverse hepatic events were observed, leading to a boxed warning for hepatotoxicity and detailed label prescriber guidelines for liver monitoring. As part of postapproval regulatory commitments, a cohort study was conducted to assess prescriber compliance with liver monitoring guidelines. METHODS: Over a 4-year period, a distributed network approach was used across 3 databases: US Veterans Affairs Healthcare System, a US outpatient oncology community practice database, and the Dutch PHARMO Database Network...
April 20, 2017: Journal of Patient Safety
https://www.readbyqxmd.com/read/28430162/ameliorative-effects-and-possible-molecular-mechanism-of-action-of-black-ginseng-panax-ginseng-on-acetaminophen-mediated-liver-injury
#9
Jun-Nan Hu, Zhi Liu, Zi Wang, Xin-Dian Li, Lian-Xue Zhang, Wei Li, Ying-Ping Wang
Background: Frequent overdosing of acetaminophen (APAP) has become the major cause of acute liver injury (ALI). The present study aimed to evaluate the potential hepatoprotective effects of black ginseng (BG) on APAP-induced mice liver injuries and the underlying mechanisms of action were further investigated for the first time. Methods: Mice were treated with BG (300, 600 mg/kg) by oral gavage once a day for seven days. On the 7th day, all mice were treated with 250 mg/kg APAP which caused severe liver injury after 24 h and hepatotoxicity was assessed...
April 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28429935/saponins-ginsenosides-from-the-leaves-of-panax-quinquefolius-ameliorated-acetaminophen-induced-hepatotoxicity-in-mice
#10
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/28428777/lactobacillus-fermentum-postbiotic-induced-autophagy-as-potential-approach-for-treatment-of-acetaminophen-hepatotoxicity
#11
Miroslav Dinić, Jovanka Lukić, Jelena Djokić, Marina Milenković, Ivana Strahinić, Nataša Golić, Jelena Begović
The aim of this study was to investigate the potential of postbiotics originated from Lactobacillus fermentum BGHV110 strain (HV110) to counteract acetaminophen (APAP)-induced hepatotoxicity in HepG2 cells. This strain was selected according to its autophagy inducing potential, based on previous studies reporting protective role of autophagy in APAP caused cellular damage. Cell viability was assessed using MTT and LDH assays, while autophagy was monitored by qPCR analysis of BECN1, Atg5, p62/SQSTM1, and PINK1 mRNA expression and by Western blot analysis of p62/SQSTM1 and lipidated LC3 accumulation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28427912/hepataprotective-effects-of-ginsenoside-rg1-a-review
#12
REVIEW
Yan Gao, Shifeng Chu, Zhao Zhang, Naihong Chen
BACKGROUND AND ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng has been used as efficient tonic and for the treatment of various diseases including hepatic disorders. Ginseng saponins, also known as ginsenosides, are principal constituents and have been treated to be responsible for disparate ginseng health benefits. The current review mainly focuses on ginsenoside Rg1, a compound isolated from traditional Chinese herbal medicine Panax ginseng Meyer. AIMS: To summary the hepataprotective effects and related mechanisms of ginsenoside Rg1, we conclude this review by combining the literature and our own researches...
April 17, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28425350/metabolomics-approach-discriminates-toxicity-index-of-pyrazinamide-and-its-metabolic-products-pyrazinoic-acid-and-5-hydroxy-pyrazinoic-acid
#13
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/28425042/arsenic-trioxide-induced-rhabdomyolysis-a-rare-but-severe-side-effect-in-an-apl-patient-a-case-report
#14
Haiyan He, Ran An, Jian Hou, Weijun Fu
Arsenic trioxide (ATO), a component of the traditional Chinese medicine arsenic sublimate, promotes apoptosis and induces leukemic cell differentiation. Combined with all-trans-retinotic acid (ATRA), ATO has become the first-line induction therapy in treating acute promyelocytic leukemia (APL). The most common side effects of ATO include hepatotoxicity, gastrointestinal symptoms, water-sodium retention, and nervous system damage. In this report, we present a rare side effect, rhabdomyolysis, in a 68-year-old female APL patient who was treated with ATO...
April 19, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28424943/intestinal-alkaline-phosphatase-attenuates-alcohol-induced-hepatosteatosis-in-mice
#15
Sulaiman R Hamarneh, Byeong-Moo Kim, Kanakaraju Kaliannan, Sara A Morrison, Tyler J Tantillo, Qingsong Tao, Mussa M Rafat Mohamed, Juan M Ramirez, Aaron Karas, Wei Liu, Dong Hu, Abeba Teshager, Sarah Shireen Gul, Konstantinos P Economopoulos, Atul K Bhan, Madhu S Malo, Michael Y Choi, Richard A Hodin
BACKGROUND AND AIMS: Bacterially derived factors from the gut play a major role in the activation of inflammatory pathways in the liver and in the pathogenesis of alcoholic liver disease. The intestinal brush-border enzyme intestinal alkaline phosphatase (IAP) detoxifies a variety of bacterial pro-inflammatory factors and also functions to preserve gut barrier function. The aim of this study was to investigate whether oral IAP supplementation could protect against alcohol-induced liver disease...
April 19, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28423281/moringa-olifera-leaves-aqueous-extract-ameliorates-hepatotoxicity-in-alloxan-induced-diabetic-rats
#16
Mabrouk Attia Abd Eldaim, Ahmed Shaban, Samy Abd Elaziz
This study was carried out to evaluate the possible mechanisms through which the Moringa oleifera leaves aqueous extract reveals its hepatoprotective effects in alloxan induced diabetic rats. Eighty albino rats were assigned into four groups. The control group was given sterile saline. The second group was injected with alloxan (150 mg/kg BW) i.p. The third group was given Moringa oleifera leaves aqueous extract (250 mg/kg BW) orally daily. The fourth group was injected with alloxan as the second group and administrated Moringa oleifera leaves aqueous extract as in the third group...
April 19, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28422390/naringin-abates-adverse-effects-of-cadmium-mediated-hepatotoxicity-an-experimental-study-using-hepg2-cells
#17
Visesh Kumar Rathi, Shubhankar Das, Archana Parampalli Raghavendra, Bola Sadashiva Satish Rao
This study investigated the protective potential of Naringin (NIN) against cadmium chloride (CdCl2 ) mediated hepatotoxicity using human hepatocellular carcinoma (HepG2) cells. An optimal concentration of NIN (5 μM) was potent enough to confer cytoprotection against CdCl2 (50 μM) as was observed by MTT assay. Preconditioning with NIN maintained redox homeostasis, mitochondrial membrane potential, and reduced apoptosis as marked by decrease in the percentage sub-G0 /G1 and Annexin V-FITC/propidium iodide positive cells (apoptotic)...
April 19, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28422377/intraperitoneal-gardiquimod-protects-against-hepatotoxicity-through-inhibition-of-oxidative-stress-and-inflammation-in-mice-with-sepsis
#18
Suqian Guo, Yu Zhang, Zhifen Wang, Yonghao Yu, Guolin Wang
Many reports recapitulate the contribution of reactive oxygen species (ROS) over-accumulation to the organ damage; it is of significance to strictly target ROS production. In this study, we evaluated the potential role of TLR7 agonist gardiquimod (GDQ) in oxidative stress (OS) in liver injury induced by sepsis. Here, we observed that intraperitoneal pretreatment with GDQ dramatically elevated the septic survival rate and effectively attenuated the septic liver injury. Interestingly, the increased ROS and inflammatory factor IL-6 levels were reversed after GDQ intervention...
April 19, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28422374/significant-curative-functions-of-the-mesenchymal-stem-cells-on-methotrexate-induced-kidney-and-liver-injuries-in-rats
#19
Amany M Gad, Wedad A Hassan, Ebtehal Mohammad Fikry
Mesenchymal stem cells (MSCs) curative effects on methotrexate (MTX)-induced kidney and liver injuries remain elusive. Therefore, rats were divided into five groups, rats received MTX orally (14 mg/kg) as a single dose/week for 2 weeks, groups 3 and 4 were injected once with 2 × 10(6) cells bone marrow MSCs and adipose-derived MSCs, respectively. The last group administered dexamethasone (DEX) (0.5 mg/kg, p.o) for 7 days. MTX caused marked increase in malondialdehyde and nitrite/nitrate concentrations...
April 19, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28422076/zeglobaltox-an-innovative-approach-to-address-organ-drug-toxicity-using-zebrafish
#20
Carles Cornet, Simone Calzolari, Rafael Miñana-Prieto, Sylvia Dyballa, Els van Doornmalen, Helma Rutjes, Thierry Savy, Davide D'Amico, Javier Terriente
Toxicity is one of the major attrition causes during the drug development process. In that line, cardio-, neuro-, and hepatotoxicities are among the main reasons behind the retirement of drugs in clinical phases and post market withdrawal. Zebrafish exploitation in high-throughput drug screening is becoming an important tool to assess the toxicity and efficacy of novel drugs. This animal model has, from early developmental stages, fully functional organs from a physiological point of view. Thus, drug-induced organ-toxicity can be detected in larval stages, allowing a high predictive power on possible human drug-induced liabilities...
April 19, 2017: International Journal of Molecular Sciences
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