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Drug-induced hepatotoxicity

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https://www.readbyqxmd.com/read/29778019/phoenix-dactylifera-protects-against-oxidative-stress-and-hepatic-injury-induced-by-paracetamol-intoxication-in-rats
#1
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/29774767/the-role-of-hepatic-antioxidant-capacity-and-hepatobiliary-transporter-in-liver-injury-induced-by-isopsoralen-in-zebrafish-larvae
#2
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/29768055/age-related-effect-of-aerobic-exercise-training-on-antioxidant-and-oxidative-markers-in-the-liver-challenged-by-doxorubicin-in-rats
#3
Mehdi Ahmadian, Valiollah Dabidi Roshan, Anthony S Leicht
The aims of the current study were to investigate the oxidant and antioxidant status of liver tissue challenged by doxorubicin and to examine the possible protective effects of aerobic exercise on doxorubicin-induced oxidative stress. Seventy-two rats were divided into three age groups (Young, Adult, and Elderly) with three treatment subgroups consisting of eight rats per age group: doxorubicin, aerobic exercise + doxorubicin, and aerobic exercise + saline. The experimental groups performed regular treadmill running for 3 weeks...
May 16, 2018: Free Radical Research
https://www.readbyqxmd.com/read/29765215/in-vivo-investigation-on-the-chronic-hepatotoxicity-induced-by-intraperitoneal-administration-of-10-nm-silicon-dioxide-nanoparticles
#4
Mansour Almansour, Saud Alarifi, Bashir Jarrar
Background: Silicon dioxide (silica) nanoparticles (SDNPs) are widely used in nanotechnology and medicine, but these nanomaterials may carry a high risk for human health while little is known about their toxicity. Methods: We investigated the alterations in morphometry, biochemistry, hematology, histology of liver tissue and gene expression of drug-metabolizing enzymes induced by 10-nm SDNPs. Healthy male Wistar albino rats were exposed to 20, 35 and 50 repeated injections of SDNPs (2 mg/kg body weight)...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29761566/nanomaterial-based-organelles-protect-normal-cells-against-chemotherapy-induced-cytotoxicity
#5
Ruibo Zhao, Xueyao Liu, Xinyan Yang, Biao Jin, Changyu Shao, Weijia Kang, Ruikang Tang
Chemotherapy-induced cytotoxicity in normal cells and organs triggers undesired lesions. Although targeted delivery is used extensively, more than half of the chemotherapy dose still concentrates in normal tissues, especially in the liver. Enabling normal cells or organs to defend against cytotoxicity represents an alternative method for improving chemotherapy. Herein, rationally designed nanomaterials are used as artificial organelles to remove unexpected cytotoxicity in normal cells. Nanocomposites of gold-oligonucleotides (Au-ODN) can capture intracytoplasmic doxorubicin (DOX), a standard chemotherapy drug, blocking the drug's access into the cell nucleus...
May 15, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29761207/omics-based-responses-induced-by-bosentan-in-human-hepatoma-heparg-cell-cultures
#6
Robim M Rodrigues, Laxmikanth Kollipara, Umesh Chaudhari, Agapios Sachinidis, René P Zahedi, Albert Sickmann, Annette Kopp-Schneider, Xiaoqi Jiang, Hector Keun, Jan Hengstler, Marlies Oorts, Pieter Annaert, Eef Hoeben, Eva Gijbels, Joery De Kock, Tamara Vanhaecke, Vera Rogiers, Mathieu Vinken
Bosentan is well known to induce cholestatic liver toxicity in humans. The present study was set up to characterize the hepatotoxic effects of this drug at the transcriptomic, proteomic, and metabolomic levels. For this purpose, human hepatoma-derived HepaRG cells were exposed to a number of concentrations of bosentan during different periods of time. Bosentan was found to functionally and transcriptionally suppress the bile salt export pump as well as to alter bile acid levels. Pathway analysis of both transcriptomics and proteomics data identified cholestasis as a major toxicological event...
May 14, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29760366/-contribution-of-chimeric-mice-with-a-humanized-liver-to-the-evaluation-of-pharmacology-toxicity-and-pharmacokinetics-in-drug-discovery-and-development
#7
Seigo Sanoh, Shigeru Ohta
To develop new drugs with high efficacy and safety, it is important to predict the pharmacological, toxicological, and pharmacokinetic profiles of drug candidates in humans. Chimeric mice with a humanized liver are mice in which human hepatocytes have been transplanted, such that mouse liver cells are replaced with human hepatocytes; these mice have been used as prediction models. Studies performed thus far indicate that chimeric mice with a humanized liver can be used for the prediction of human-specific metabolite formation and plasma concentration-time curves for several drugs...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29755557/evaluation-of-silibinin-effects-on-the-viability-of-hepg2-human-hepatocellular-liver-carcinoma-and-huvec-human-umbilical-vein-endothelial-cell-lines
#8
Niki Vakili Zahir, Maryam Nakhjavani, Parastoo Hajian, Farshad H Shirazi, Hamidreza Mirzaei
Human hepatocellular carcinoma is one of the most common recurrent malignancies since there is no effective therapy for it. Silibinin, a widely used drug and supplement for various liver disorders, demonstrated anti-cancer effects on human hepatocellular carcinoma, human prostate adenocarcinoma cells, human breast carcinoma cells, human ectocervical carcinoma cells, and human colon cancer cells. Considering the anti-hepatotoxic activity of silibinin and its strong preventive and anti-cancer efficacy against various epithelial cancers, we investigated the efficacy of silibinin against human HCC and HUVEC cell lines...
2018: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/29753871/combinatorial-usage-of-fungal-polysaccharides-from-cordyceps-sinensis-and-ganoderma-atrum-ameliorate-drug-induced-liver-injury-in-mice
#9
Songtao Fan, Xiaojun Huang, Sunan Wang, Chang Li, Zhihong Zhang, Mingyong Xie, Shaoping Nie
This study investigated the possible protective effect of combined fungal polysaccharides (CFP), consisting of Cordyceps sinensis polysaccharides (CSP) and Ganoderma atrum polysaccharides (PSG) with well-defined structural characteristics, against cyclophosphamide (CTX)-induced hepatotoxicity in mice. Our results indicated CFP effectively prevented the liver injury by decreasing toxicity markers (aspartate transaminase, alanine aminotransferase and alkaline phosphatase). Further biochemical and molecular analysis indicated CSP particularly inhibited the activation of Toll-like receptor 9 (TLR9) and its related inflammatory signals, including pro-inflammatory cytokines, inducible nitric oxide synthase, and cyclooxygenase-2 to modulate hepatic inflammation response...
May 10, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29753208/mechanisms-of-acetaminophen-induced-liver-injury-and-its-implications-for-therapeutic-interventions
#10
REVIEW
Mingzhu Yan, Yazhen Huo, Shutao Yin, Hongbo Hu
Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in many developed countries. Mitochondrial oxidative stress is considered to be the predominant cellular event in APAP-induced liver injury. Accordingly, N-acetyl cysteine, a known scavenger of reactive oxygen species (ROS), is recommended as an effective clinical antidote against APAP-induced acute liver injury (AILI) when it is given at an early phase; however, the narrow therapeutic window limits its use. Hence, the development of novel therapeutic approaches that can offer broadly protective effects against AILI is clearly needed...
April 22, 2018: Redox Biology
https://www.readbyqxmd.com/read/29751151/different-administration-patterns-of-docosahexaenoic-acid-in-combating-cytotoxic-manifestations-due-to-arsenic-trioxide-acute-promyelocytic-leukemia-drug-induced-redox-imbalance-in-hepatocytes
#11
S Abhilash, R Siviyasankar, P Binu, P Arathi, R Harikumaran Nair
Docosahexaenoic acid (DHA) obtained from fish and plant sources is an essential dietary fatty acid and an important cell membrane structural component. The acute promyelocytic leukemia (APL) drug arsenic trioxide (As2 O3 ), causes hepatotoxicity. We evaluated the protective potential of DHA as pre/ combination/ post-administration patterns against As2 O3 induced toxicity. The therapeutic concentration of As2 O3 (10 µM) resulted in cytotoxicity with a significant (p < 0.05) variation from the control group...
May 8, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29748533/p53-attenuates-acetaminophen-induced-hepatotoxicity-by-regulating-drug-metabolizing-enzymes-and-transporter-expression
#12
Jiahong Sun, Yajie Wen, Yanying Zhou, Yiming Jiang, Yixin Chen, Huizheng Zhang, Lihuan Guan, Xinpeng Yao, Min Huang, Huichang Bi
Acetaminophen (APAP) overdose is the most frequent cause of drug-induced acute liver failure. Inhibition of APAP metabolic activation and promotion in APAP disposition are important to protect against APAP-induced liver injury. Tumor suppressor p53 is traditionally recognized as a surveillance molecule to preserve genome integrity. Recent studies have emerged on discovering its functions in metabolic regulation. Our previous study reported that p53 promoted bile acid disposition and alleviated cholestastic syndrome...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29744119/levetiracetam-induced-transaminitis-in-a-young-male-with-traumatic-brain-injury
#13
Vivekananda Rachamallu, Michael M Song, Jace M Reed, Manish Aligeti
Levetiracetam is a commonly prescribed antiepileptic drug for seizure prophylaxis in patients with traumatic brain injury (TBI). Levetiracetam metabolism has been reported to be non-dependent on hepatic cytochrome P450 (CYP450) isoenzyme system. Furthermore, levetiracetam and its metabolites are reported to be eliminated from systemic circulation via renal excretion. Therefore, due to its well-known renal clearance mechanism with no dosage adjustments recommended for hepatic impairment, levetiracetam is often chosen as the drug of choice in patients with suspected or ongoing hepatic dysfunction...
November 2017: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/29743445/increased-susceptibility-to-troglitazone-induced-mitochondrial-permeability-transition-in-type-2-diabetes-mellitus-model-rat
#14
Masahiro Segawa, Shuichi Sekine, Tomoyuki Sato, Kousei Ito
Troglitazone, a member of the thiazolidinedione class of antidiabetic drugs, was withdrawn from the market because it causes severe liver injury. One of the mechanisms for this adverse effect is thought to be mitochondrial toxicity. To investigate the characteristics of troglitazone-induced liver toxicity in more depth, the toxicological effects of troglitazone on hepatocytes and liver mitochondria were investigated using a rat model of type 2 diabetes mellitus (T2DM). Troglitazone was found to increase mitochondrial permeability transition (MPT) in the liver mitochondria of diabetic rats to a greater extent than in control rats, whereas mitochondrial membrane potential and oxidative phosphorylation were not affected...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29735688/cisplatin-dna-adduct-repair-of-transcribed-genes-is-controlled-by-two-circadian-programs-in-mouse-tissues
#15
Yanyan Yang, Ogun Adebali, Gang Wu, Christopher P Selby, Yi-Ying Chiou, Naim Rashid, Jinchuan Hu, John B Hogenesch, Aziz Sancar
Cisplatin is a major cancer chemotherapeutic drug. It kills cancer cells by damaging their DNA, mainly in the form of Pt-d(GpG) diadducts. However, it also has serious side effects, including nephrotoxicity and hepatotoxicity that limit its usefulness. Chronotherapy is taking circadian time into account during therapy to improve the therapeutic index, by improving efficacy and/or limiting toxicity. To this end, we tested the impact of clock time on excision repair of cisplatin-induced DNA damage at single-nucleotide resolution across the genome in mouse kidney and liver...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29722569/exacerbated-liver-injury-of-antithyroid-drugs-in-endotoxin-treated-mice
#16
Reza Heidari, Fatemeh Ahmadi, Hamid Reza Rahimi, Negar Azarpira, Massood Hosseinzadeh, Asma Najibi, Hossein Niknahad
Drug-induced liver injury is a major concern in clinical studies as well as in post-marketing surveillance. Previous evidence suggested that drug exposure during periods of inflammation could increase an individual's susceptibility to drug hepatoxicity. The antithyroid drugs, methimazole (MMI) and propylthiouracil (PTU) can cause adverse reactions in patients, with liver as a usual target. We tested the hypothesis that MMI and PTU could be rendered hepatotoxic in animals undergoing a modest inflammation. Mice were treated with a nonhepatotoxic dose of LPS (100 µg/kg, i...
May 3, 2018: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29722540/impact-of-physicochemical-properties-on-dose-and-hepatotoxicity-of-oral-drugs
#17
Paul D Leeson
A database containing maximum daily doses of 1841 marketed oral drugs was used to examine the influence of physicochemical properties on dose and hepatotoxicity (drug induced liver injury, DILI). Drugs in the highest ~20% dose range had significantly reduced mean lipophilicity and molecular weight, increased fractional surface area, increased % of acids and decreased % of bases, versus drugs in the lower ~60% dose range. Drugs in the ~20-40% dose range had intermediate mean properties, similar to the mean values for the full drug set...
May 3, 2018: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29722533/advancing-predictive-hepatotoxicity-at-the-intersection-of-experimental-in-silico-and-artificial-intelligence-technologies
#18
Keith Fraser, Dylan M Bruckner, Jonathan S Dordick
Adverse drug reactions (ADRs), particularly those that result in drug-induced liver injury (DILI) is a major cause of drug failure in clinical trials and drug withdrawals. Hepatotoxicity-mediated drug attrition occurs despite substantial investments of time and money in developing cellular assays, animal models and computational models to predict its occurrence in humans. Underperformance in predicting hepatotoxicity associated with drugs and drug candidates has been attributed to existing gaps in our understanding of the mechanisms involved in driving hepatic injury after these compounds perfuse and are metabolized by the liver...
May 3, 2018: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29722039/mortality-from-adverse-drug-reaction-related-hospitalizations-in-south-west-ethiopia-a-cross-sectional-study
#19
M T Angamo, L Chalmers, C M Curtain, D Yilma, L Bereznicki
WHAT IS KNOWN AND OBJECTIVE: Adverse drug reactions (ADRs) are an important cause of mortality during medical care. To our knowledge, no Ethiopian studies have reported on mortality due to ADRs in patients presenting to hospital from the community setting. The aim of this study was to determine the mortality rate attributable to ADRs in patients presenting to hospital, identify drugs implicated in the ADR-related deaths and identify factors contributing to ADR-related mortality at Jimma University Specialised Hospital (JUSH), south-west Ethiopia METHODS: This cross-sectional study included 1001 patients aged ≥18 years consecutively admitted to medical wards from May 2015 to August 2016...
May 2, 2018: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29721756/successful-oral-desensitization-with-osimertinib-following-osimertinib-induced-fever-and-hepatotoxicity-a-case-report
#20
Ryosuke Hirabayashi, Daichi Fujimoto, Yukari Satsuma, Masaki Hirabatake, Keisuke Tomii
Osimertinib is a standard second-line therapy for patients who develop EGFR Thr790Met resistance mutation after treatment with first-line epidermal growth factor receptor tyrosine kinase inhibitors. Although no other effective targeted treatment option exists for these patients, osimertinib might be permanently discontinued owing to the onset of severe drug-induced toxicities like hepatotoxicity. Herein, we report a case of successful oral desensitization with osimertinib after the patient developed osimertinib-induced fever and hepatotoxicity...
May 2, 2018: Investigational New Drugs
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