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Drug-induced hepatotoxicity

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https://www.readbyqxmd.com/read/28448868/protective-effects-of-teucrium-polium-aqueous-extract-and-ascorbic-acid-on-hematological-and-some-biochemical-parameters-against-carbon-tetrachloride-ccl4-induced-toxicity-in-rats
#1
Fatma Rahmouni, Latifa Hamdaoui, Riadh Badraoui, Tarek Rebai
Herbal drugs play a crucial function to protect organisms from the toxic effect of some compounds. The present study was designed to evaluate the protective effects of Teucrium Polium (TP) aqueous extract and vitamin C (Vit C) against carbon tetrachloride (CCl4) which induced toxicity in rats. Male albino Wistar rats were divided into six groups: group I was used as controls, group II received CCl4 in olive oil (0.5ml/kg) by gavage, and group III received CCl4 in olive oil (0.5ml/kg) by gavage after three days of receiving TP (5g/l), orally, for seven days; Group IV received TP (5g/l) alone, orally, for seven days, Group V received CCl4 in olive oil (0...
April 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28448553/a-computational-toxicogenomics-approach-identifies-a-list-of-highly-hepatotoxic-compounds-from-a-large-microarray-database
#2
Héctor A Rueda-Zárate, Iván Imaz-Rosshandler, Roberto A Cárdenas-Ovando, Juan E Castillo-Fernández, Julieta Noguez-Monroy, Claudia Rangel-Escareño
The liver and the kidney are the most common targets of chemical toxicity, due to their major metabolic and excretory functions. However, since the liver is directly involved in biotransformation, compounds in many currently and normally used drugs could affect it adversely. Most chemical compounds are already labeled according to FDA-approved labels using DILI-concern scale. Drug Induced Liver Injury (DILI) scale refers to an adverse drug reaction. Many compounds do not exhibit hepatotoxicity at early stages of development, so it is important to detect anomalies at gene expression level that could predict adverse reactions in later stages...
2017: PloS One
https://www.readbyqxmd.com/read/28443154/drug-induced-liver-injury-do-we-know-everything
#3
REVIEW
Tamara Alempijevic, Simon Zec, Tomica Milosavljevic
Interest in drug-induced liver injury (DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged...
April 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28438569/methylprednisolone-liver-toxicity-a-new-case-and-a-french-regional-pharmacovigilance-survey
#4
Jérôme Dumortier, Judith Cottin, Caroline Lavie, Olivier Guillaud, Valérie Hervieu, Christine Chambon-Augoyard, Jean-Yves Scoazec, Sandra Vukusic, Thierry Vial
Reported hepatotoxicity induced by corticosteroids is very rare, and the diagnosis is highly challenging in the context of auto-immune disease. We report here a case of high-dose methylprednisolone (MP)-induced acute hepatitis confirmed by liver histology in a patient with multiple sclerosis (MS) and a case series (n=4) notified to the French Pharmacovigilance center of Lyon. In all 5 cases, other common causes of hepatitis were excluded. The causal relationship with MP pulse therapy was supported by the fact that MP was the only culprit drug...
April 21, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28436314/metabolomic-approaches-in-the-discovery-of-potential-urinary-biomarkers-of-drug-induced-liver-injury-dili
#5
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/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/28429935/saponins-ginsenosides-from-the-leaves-of-panax-quinquefolius-ameliorated-acetaminophen-induced-hepatotoxicity-in-mice
#7
Xing-Yue Xu, Jun-Nan Hu, Zhi Liu, Rui Zhang, Yu-Fang He, Wei Hou, Zhi-Qing Wang, Ge Yang, Wei Li
Acetaminophen (APAP) overdose is one of the most common inducements of drug-induced liver injury (DILI) in the world. The main purpose of this paper was to investigate the liver protection activity of saponins (ginsenosides) from the leaves of Panax quinquefolius (PQS) against APAP-induced hepatotoxicity, and the involved mechanisms were demonstrated for the first time. Mice were pretreated with PQS (150 and 300 mg/kg) by oral gavage for 7 days before being treated with 250 mg/kg APAP. Severe liver injury was exerted at 24 h post-APAP, and hepatotoxicity was assessed...
April 25, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28427912/hepataprotective-effects-of-ginsenoside-rg1-a-review
#8
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
#9
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/28422076/zeglobaltox-an-innovative-approach-to-address-organ-drug-toxicity-using-zebrafish
#10
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
https://www.readbyqxmd.com/read/28421385/in-vitro-and-in-vivo-anti-tumor-effects-of-selected-platinum-iv-and-dinuclear-platinum-ii-complexes-against-lung-cancer-cells
#11
Milos Arsenijevic, Marija Milovanovic, Snezana Jovanovic, Natalija Arsenijevic, Bojana Simovic Markovic, Marina Gazdic, Vladislav Volarevic
In the present study, cytotoxic effects of cisplatin, the most usually used chemotherapeutic agent, were compared with new designed platinum(IV) ([PtCl4(en)] (en = ethylenediamine) and [PtCl4(dach)]) (dach = (±)-trans-1,2-diaminocyclohexane) and platinum(II) complexes ([{trans-Pt(NH3)2Cl}2(μ-pyrazine)](ClO4)2 (Pt1), [{trans-Pt(NH3)2Cl}2(μ-4,4'-bipyridyl)](ClO4)2DMF(Pt2),[{trans-Pt(NH3)2Cl}2(μ-1,2-bis(4pyridyl)ethane)](ClO4)2 (Pt3)), in vitro and in vivo against human and murine lung cancer cells, to determine anti-tumor potential of newly synthesized platinum-based drugs in the therapy of lung cancer...
April 18, 2017: Journal of Biological Inorganic Chemistry: JBIC
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
#12
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/28416868/a-synergistic-effect-of-cremophor-and-beta-glucosylceramide-to-exert-liver-and-sugar-protection
#13
Yehudit Shabat, Yaron Ilan
Many commonly used drugs carry the potential to induce hepatotoxicity, and a large number of foods and beverages induce an increase in blood sugar levels. A change in lifestyle by omitting these compounds is not applicable in many circumstances. β-Glucosylceramide (GC) is a naturally occurring glycosphingolipid that exerts an effect on the immune system. Cremophor EL (CrEL) is a synthetic, nonionic surfactant that is used as a vehicle for the administration of water-insoluble compounds. The aim of the present study was to determine the synergistic effect of oral administration of the combination of GC and CrEL (GCC) when added to potential toxic substrates or to sugar-enriched compounds...
April 2017: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/28414177/the-acitretin-and-methotrexate-combination-therapy-for-psoriasis-vulgaris-achieves-higher-effectiveness-and-less-liver-fibrosis
#14
Jingang An, Dingwei Zhang, Jiawen Wu, Jiong Li, Xiu Teng, Xiaomin Gao, Ruilian Li, Xiuying Wang, Linlin Xia, Yumin Xia
Both acitretin and methotrexate are effective in ameliorating psoriatic lesion. However, their combination has been seldom reported in the treatment of psoriasis because of the warning regarding the potential hepatotoxicity of the drug interactions. This study was designed to investigate the effectiveness of such combination therapy for psoriasis vulgaris, and the potential benefit as well as side effect during the treatment. Thirty-nine patients with psoriasis vulgaris were treated with acitretin, methotrexate or their combination or as control...
April 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28412648/content-decline-of-serca-inhibitors-saikosaponin-a-and-d-attenuates-cardiotoxicity-and-hepatotoxicity-of-vinegar-baked-radix-bupleuri
#15
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/28409500/tissue-protective-activity-of-selenomethionine-and-d-panthetine-in-b16-melanoma-bearing-mice-under-doxorubicin-treatment-is-not-connected-with-their-ros-scavenging-potential
#16
Rostyslav R Panchuk, Nadia R Skorokhyd, Yuliya S Kozak, Liliya V Lehka, Andrey G Moiseenok, Rostyslav S Stoika
AIM: To evaluate molecular mechanisms of tissue-protective effects of antioxidants selenomethionine (SeMet) and D-pantethine (D-Pt) applied in combination with doxorubicin (Dx) in B16 melanoma-bearing-mice. METHODS: Impact of the chemotherapy scheme on a survival of tumor-bearing animals, general nephro- and hepatotoxicity, blood cell profile in vivo, and ROS content in B16 melanoma cells in vitro was compared with the action of Dx applied alone. Nephrotoxicity of the drugs was evaluated by measuring creatinine indicator assay, hepatotoxicity was studied by measuring the activity of ALT/AST enzymes, and myelotoxicity was assessed by light microscopic analysis of blood smears...
April 14, 2017: Croatian Medical Journal
https://www.readbyqxmd.com/read/28398814/management-of-hepatotoxicity-induced-by-the-use-of-olanzapine
#17
Yunus Emre Dönmez, Özlem Özcan, Nusret Soylu, Fatma Kartal Sarıoğlu, Ayşe Selimoğlu
Numerous drugs cause hepatotoxicity clinically or biologically. Neuropsychiatric drugs constitute 16% of these drugs. The occurrence of hepatotoxicity induced by the use of olanzapine is expressed by the researchers. In such cases, generally the dose of olanzapine is reduced or the drug is completely discontinued and the treatment of the patient fails. The aim of this study is to report the case for whom elevated liver enzymes were observed but the process was managed without changing treatment dose and drug and to discuss this case with literature information...
April 2017: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/28389387/association-of-cyp2b6-gene-polymorphisms-and-anti-tuberculosis-drug-induced-hepatotoxicity-in-a-chinese-population
#18
Yu Wang, Xi Xiang, Shou-Quan Wu, Guo Chen, Miao-Miao Zhang, Ming-Gui Wang, Feng-Juan Wang, Andrew J Sandford, Jian-Qing He
OBJECTIVES: Antituberculosis drug-induced hepatotoxicity (ATDH) remains a common and severe challenge in tuberculosis (TB) chemotherapy. A growing number of studies have revealed that genetic polymorphisms affect an individual's susceptibility to ATDH. The aim of this study was to explore the role of cytochrome P450 family 2 subfamily B member 6 (CYP2B6) gene polymorphisms in the development of ATDH in Chinese TB patients. METHODS: CYP2B6*6 genotypes were determined in TB patients with and without ATDH...
April 5, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28388864/clinical-and-histologic-features-of-azathioprine-induced-hepatotoxicity
#19
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/28388302/genome-wide-association-and-replication-study-of-hepatotoxicity-induced-by-antiretrovirals-alone-or-with-concomitant-anti-tuberculosis-drugs
#20
Zelalem Petros, Ming Ta Michael Lee, Atsushi Takahashi, Yanfei Zhang, Getnet Yimer, Abiy Habtewold, Ina Schuppe-Koistinen, Taisei Mushiroda, Eyasu Makonnen, Michiaki Kubo, Eleni Aklillu
Drug-induced hepatotoxicity (DIH) is a common adverse event that is associated with both antiretroviral (ARV) and anti-tuberculosis drugs (ATD). Moreover, the genetic variations predisposing ARV- and ARV-ATD-induced liver toxicity in African populations are not well investigated, despite the two diseases being the major global health problems in sub-Saharan Africa. We performed a genome-wide association study (GWAS) and replication study to identify the genetic variants linked to the risk of developing DIH due to ARV drugs alone, and ARV-ATD co-treatment in Ethiopian HIV-positive patients...
April 2017: Omics: a Journal of Integrative Biology
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