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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/29777724/novel-mirna-biomarkers-for-genotoxicity-screening-in-mouse
#2
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/29774767/the-role-of-hepatic-antioxidant-capacity-and-hepatobiliary-transporter-in-liver-injury-induced-by-isopsoralen-in-zebrafish-larvae
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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/29748443/a-phase-2-multicenter-study-of-the-anti-cd19-antibody-drug-conjugate-coltuximab-ravtansine-sar3419-in-patients-with-relapsed-or-refractory-diffuse-large-b-cell-lymphoma-previously-treated-with-rituximab-based-immunotherapy
#14
Marek Trněný, Gregor Verhoef, Martin Js Dyer, Dina Ben Yehuda, Caterina Patti, Miguel Canales, Andrés Lopez, Farrukh T Awan, Paul G Montgomery, Andrea Janikova, Anna M Barbui, Kazimierz Sulek, Maria J Terol, John Radford, Anna Guidetti, Massimo Di Nicola, Laure Siraudin, Laurence Hatteville, Sandrine Schwab, Corina Oprea, Alessandro M Gianni
This phase 2, single-arm, multicenter study examined the efficacy and safety of coltuximab ravtansine (an anti-CD19 antibody drug conjugate) in 61 patients with histologically documented (de novo or transformed) relapsed or refractory diffuse large B-cell lymphoma who had previously received rituximab containing immuno-chemotherapy. Patients had received a median of 2.0 (range 0-9) prior treatment regimens for diffuse large B-cell lymphoma and almost half (45.9%) had bulky disease (≥ lesion >5 cm) at trial entry...
May 10, 2018: Haematologica
https://www.readbyqxmd.com/read/29746543/automated-assessment-of-steatosis-in-murine-fatty-liver
#15
Deepak Sethunath, Siripriya Morusu, Mihran Tuceryan, Oscar W Cummings, Hao Zhang, Xiao-Ming Yin, Scott Vanderbeck, Naga Chalasani, Samer Gawrieh
Although mice are commonly used to study different aspects of fatty liver disease, currently there are no validated fully automated methods to assess steatosis in mice. Accurate detection of macro- and microsteatosis in murine models of fatty liver disease is important in studying disease pathogenesis and detecting potential hepatotoxic signature during drug development. Further, precise quantification of macrosteatosis is essential for quantifying effects of therapies. Here, we develop and validate the performance of automated classifiers built using image processing and machine learning methods for detection of macro- and microsteatosis in murine fatty liver disease and study the correlation of automated quantification of macrosteatosis with expert pathologist's semi-quantitative grades...
2018: PloS One
https://www.readbyqxmd.com/read/29744119/levetiracetam-induced-transaminitis-in-a-young-male-with-traumatic-brain-injury
#16
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
#17
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
#18
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
#19
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
#20
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
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