keyword
MENU ▼
Read by QxMD icon Read
search

drug induced liver toxicity

keyword
https://www.readbyqxmd.com/read/28527127/evaluation-of-heparg-cells-for-the-assessment-of-indirect-drug-induced-hepatotoxicity-using-inh-as-a-model-substance
#1
Anika Mann, Thomas Pelz, Knut Rennert, Alexander Mosig, Michael Decker, Amelie Lupp
HepaRG cells are widely used as an in vitro model to assess drug-induced hepatotoxicity. However, only few studies exist so far regarding their suitability to detect the effects of drugs requiring a preceding activation via the cytochrome P450 (CYP) system. A prototypic substance is the anti-tuberculosis agent INH, which is metabolized into N-acetylhydrazine, which then triggers hepatotoxicity. Therefore, the aim of the present study was to test if this effect can also be detected in HepaRG cells and if it can be counteracted by the known hepatoprotectant silibinin...
May 19, 2017: Human Cell
https://www.readbyqxmd.com/read/28524079/assembly-of-hepatocyte-spheroids-using-magnetic-3d-cell-culture-for-cyp450-inhibition-induction
#2
Pujan K Desai, Hubert Tseng, Glauco R Souza
There is a significant need for in vitro methods to study drug-induced liver injury that are rapid, reproducible, and scalable for existing high-throughput systems. However, traditional monolayer and suspension cultures of hepatocytes are difficult to handle and risk the loss of phenotype. Generally, three-dimensional (3D) cell culture platforms help recapitulate native liver tissue phenotype, but suffer from technical limitations for high-throughput screening, including scalability, speed, and handling. Here, we developed a novel assay for cytochrome P450 (CYP450) induction/inhibition using magnetic 3D cell culture that overcomes the limitations of other platforms by aggregating magnetized cells with magnetic forces...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28512733/a-lipidomic-cell-based-assay-for-studying-drug-induced-phospholipidosis-and-steatosis
#3
Juan Carlos García-Cañaveras, Manuel David Peris-Díaz, M Isabel Alcoriza, Manuela Cerdán-Calero, M Teresa Donato, Agustín Lahoz
Phospholipidosis and steatosis are two toxic effects, which course with overaccumulation of different classes of lipids in the liver. MS-based lipidomics has become a powerful tool for the comprehensive determination of lipids. LC-MS lipid profiling of HepG2 cells is proposed as an in vitro assay to study and anticipate phospholipidosis and steatosis. Cells with and without pre-incubation with a mixture of free fatty acids (FFA) (i.e., oleic and palmitic) were exposed to a set of well-known steatogenic and phospholipidogenic compounds...
May 17, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28511910/synthesis-and-biological-research-of-novel-azaacridine-derivatives-as-potent-dna-binding-ligands-and-topoisomerase-ii-inhibitors
#4
Dan Li, Zigao Yuan, Shaopeng Chen, Cunlong Zhang, Lu Song, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
DNA and DNA-related enzymes are one of the most effective and common used intracellular anticancer targets in clinic and laboratory studies, however, most of DNA-targeting drugs suffered from toxic side effects. Development of new molecules with good antitumor activity and low side effects is important. Based on computer aided design and our previous studies, a series of novel azaacridine derivatives were synthesized as DNA and topoisomerases binding agents, among which compound 9 displayed the best antiproliferative activity with an IC50 value of 0...
May 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28505473/the-protective-study-about-alleviation-of-simvastatin-on-the-damages-of-peg-bns-in-mice
#5
Wenzhen An, Biao Han, Kang Li, Shahnaz Akhtar, Ying Zhang, Xuan Zhang, Xueli Sha, Lan Gao
Boron nitride nanoparticles have been proved to cause various toxicities, damages or inflammations after entering into in vivo in previous reports. However, up to now, there are rare investigations about the alleviation of damages caused by nanoparticles in vivo through natural small molecule drugs. Therefore, in this work, PEG-BNs with high solubility was successfully synthesized, and then their biodistribution in mice were studied using radiolabeling technique. And the heart, lung, liver, spleen, kidney tissues and blood samples were done for histology and biochemical analysis...
May 1, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28505368/farnesoid-x-receptor-protects-against-low-dose-carbon-tetrachloride-induced-liver-injury-through-the-taurocholate-jnk-pathway
#6
Shogo Takahashi, Naoki Tanaka, Srujana Golla, Tatsuki Fukami, Kristopher W Krausz, Marianne A Polunas, Blair C Weig, Yusuke Masuo, Cen Xie, Changtao Jiang, Frank J Gonzalez
Hepatotoxicity is of major concern for humans exposed to industrial chemicals and drugs. Disruption of farnesoid X receptor (FXR), a master regulator of bile acid (BA) metabolism, enhanced the sensitivity to liver injury in mice after toxicant exposure, but the precise mechanism remains unclear. In this study, the interconnection between BA metabolism, FXR, and chemically-induced hepatotoxicity was investigated using metabolomics, Fxr-null mice and hepatocytes, and adenovirus. A single low-dose intraperitoneal injection of carbon tetrachloride (CCl4), an inducer of acute hepatitis in mice, resulted in more severe hepatocyte damage and higher induction of pro-inflammatory mediators, such as chemokine (C-C motif) ligand 2 (Ccl2), in Fxr-null mice...
May 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28496041/a-rapid-mitochondrial-toxicity-assay-utilizing-rapidly-changing-cell-energy-metabolism
#7
Yosuke Sanuki, Tetsuro Araki, Osamu Nakazono, Kazuyuki Tsurui
Drug-induced liver injury is a major cause of safety-related drug-marketing withdrawals. Several drugs have been reported to disrupt mitochondrial function, resulting in hepatotoxicity. The development of a simple and effective in vitro assay to identify the potential for mitochondrial toxicity is thus desired to minimize the risk of causing hepatotoxicity and subsequent drug withdrawal. An in vitro test method called the "glucose-galactose" assay is often used in drug development but requires prior-culture of cells over several passages for mitochondrial adaptation, thereby restricting use of the assay...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28496040/induction-of-human-cytochrome-p450-3a-enzymes-in-cultured-placental-cells-by-thalidomide-and-relevance-to-bioactivation-and-toxicity
#8
Norie Murayama, Yasuhiro Kazuki, Daisuke Satoh, Kazuya Arata, Tasuku Harada, Norio Shibata, F Peter Guengerich, Hiroshi Yamazaki
Evidence has been presented for auto-induced human cytochrome P450 3A enzyme involvement in the teratogenicity and clinical outcome of thalidomide due to oxidation to 5-hydroxythalidomide and subsequent metabolic activation in livers. In this study, more relevant human placenta preparations and placental BeWo cells showed low but detectable P450 3A4/5 mRNA expression and drug oxidation activities. Human placental microsomal fractions from three subjects showed detectable midazolam 1´- and 4-hydroxylation and thalidomide 5-hydroxylation activities...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28486596/troglitazone-inhibits-bile-acid-amidation-a-possible-risk-factor-for-liver-injury
#9
Eiichiro Ogimura, Tetsuya Nakagawa, Jiro Deguchi, Shuichi Sekine, Kousei Ito, Kiyoko Bando
Troglitazone and pioglitazone were developed as thiazolidinedione-type anti-diabetes drugs, but only troglitazone was withdrawn from the markets due to severe liver injury. As both troglitazone and its sulfate metabolite are strong inhibitors of the bile salt export pump (BSEP), troglitazone-induced bile acid (BA) retention is thought to be one of the underlying mechanisms of liver injury. However, pioglitazone is also a strong BSEP inhibitor, indicating other mechanisms may also be involved in troglitazone-induced BA retention...
May 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28486401/drug-induced-liver-injury-cascade-of-events-leading-to-cell-death-apoptosis-or-necrosis
#10
REVIEW
Andrea Iorga, Lily Dara, Neil Kaplowitz
Drug-induced liver injury (DILI) can broadly be divided into predictable and dose dependent such as acetaminophen (APAP) and unpredictable or idiosyncratic DILI (IDILI). Liver injury from drug hepatotoxicity (whether idiosyncratic or predictable) results in hepatocyte cell death and inflammation. The cascade of events leading to DILI and the cell death subroutine (apoptosis or necrosis) of the cell depend largely on the culprit drug. Direct toxins to hepatocytes likely induce oxidative organelle stress (such as endoplasmic reticulum (ER) and mitochondrial stress) leading to necrosis or apoptosis, while cell death in idiosyncratic DILI (IDILI) is usually the result of engagement of the innate and adaptive immune system (likely apoptotic), involving death receptors (DR)...
May 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28479099/protective-effect-of-chlorogenic-acid-against-methotrexate-induced-oxidative-stress-inflammation-and-apoptosis-in-rat-liver-an-experimental-approach
#11
Nemat Ali, Summya Rashid, Sana Nafees, Syed Kazim Hasan, Ayaz Shahid, Ferial Majed, Sarwat Sultana
Methotrexate (MTX) is a drug which is used to treat different types of cancers but hepatotoxicity limits its clinical use. Chlorogenic acid (CGA) is one of the most abundant naturally occurring polyphenols in the human diet. Here, we assessed the effect of CGA against MTX-induced hepatotoxicity and investigated the underlying possible mechanisms in Wistar Rats. Rats were pre-treated with CGA (50 or 100 mg kg/b.w) and administered a single dose of MTX (20 mg/kg, b.w.). MTX caused hepatotoxicity as evidenced by significant increase in serum toxicity markers, histopathological changes...
May 4, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28476244/imaging-of-hepatic-toxicity-of-systemic-therapy-in-a-tertiary-cancer-centre-chemotherapy-haematopoietic-stem-cell-transplantation-molecular-targeted-therapies-and-immune-checkpoint-inhibitors
#12
REVIEW
F Alessandrino, S H Tirumani, K M Krajewski, A B Shinagare, J P Jagannathan, N H Ramaiya, D N Di Salvo
The purpose of this review is to familiarise radiologists with the spectrum of hepatic toxicity seen in the oncology setting, in view of the different systemic therapies used in cancer patients. Drug-induced liver injury can manifest in various forms, and anti-neoplastic agents are associated with different types of hepatotoxicity. Although chemotherapy-induced liver injury can present as hepatitis, steatosis, sinusoidal obstruction syndrome, and chronic parenchymal damages, molecular targeted therapy-associated liver toxicity ranges from mild liver function test elevation to fulminant life-threatening acute liver failure...
May 2, 2017: Clinical Radiology
https://www.readbyqxmd.com/read/28464411/c-glycosyl-flavonoids-from-beta-vulgaris-cicla-and-betalains-from-beta-vulgaris-rubra-antioxidant-anticancer-and-antiinflammatory-activities-a-review
#13
REVIEW
Paolino Ninfali, Elena Antonini, Alessandra Frati, Emanuele-Salvatore Scarpa
The green beet (Beta vulgaris var. cicla L.) and red beetroot (B. vulgaris var. rubra L.) contain phytochemicals that have beneficial effects on human health. Specifically, the green beet contains apigenin, vitexin, vitexin-2-O-xyloside and vitexin-2-O-rhamnoside, while the red beetroot is a source of betaxanthins and betacyanins. These phytochemicals show considerable antioxidant activity, as well as antiinflammatory and antiproliferative activities. Vitexin-2-O-xyloside, in combination with betaxanthins and betacyanins, exerts antiproliferative activity in breast, liver, colon and bladder cancer cell lines, through the induction of both intrinsic and extrinsic apoptotic pathways...
May 2, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28463418/use-of-primary-rat-hepatocytes-for-prediction-of-drug-induced-mitochondrial-dysfunction
#14
Cong Liu, Shuichi Sekine, Binbin Song, Kousei Ito
Mitochondrial dysfunction plays a central role in drug-induced liver injury. To evaluate drug-induced mitochondrial impairment, several isolated mitochondria- or cell line-based assays have been reported. Among them, culturing HepG2 cells in galactose provides a remarkable method to assess mitochondrial toxicity by activating mitochondrial aerobic respiration. We applied this assay to primary rat hepatocytes by culturing cells in galactose and hyperoxia to enhance the evaluation of metabolism-related drug-induced mitochondrial toxicity...
May 2, 2017: Current Protocols in Toxicology
https://www.readbyqxmd.com/read/28463035/inhibition-of-nf-%C3%AE%C2%BAb-tnf-%C3%AE-pathway-may-be-involved-in-the-protective-effect-of-resveratrol-against-cyclophosphamide-induced-multi-organ-toxicity
#15
Azza A El-Sheikh, Mohamed A Morsy, Ahmed M Okasha
CONTEXT: Cyclophosphamide (CyP), an efficient anticancer drug, may damage normal human cells. Resveratrol (RES), a natural polyphenol, has a diverse pharmacological properties. OBJECTIVE: To test possible protective effect of RES on multi-organ damage caused by CyP. MATERIALS AND METHODS: RES (10 mg/kg/day) was administered orally for 8 days. In independent rat groups, CyP toxicity was induced via a single dose of 150 mg/kg i.p. 3 days before the end of experiment, with or without RES treatment...
May 2, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28458453/suppressive-effects-of-the-expectorant-drug-ambroxol-hydrochloride-on-quartz-induced-lung-inflammation-in-f344-rats
#16
Shohei Kanie, Masanao Yokohira, Keiko Yamakawa, Yuko Nakano-Narusawa, Shota Yoshida, Nozomi Hashimoto, Katsumi Imaida
Surfactant proteins (SPs) are essential to respiratory structure and function. The expectorant drug ambroxol hydrochloride is clinically prescribed to stimulate pulmonary surfactant and airway serous secretion. Therefore, ambroxol hydrochloride may affect SP production and pulmonary inflammation. Lung toxicity of fine particles of various materials has been examined previously in our in vivo bioassay using the intratracheal (i.t.) instillation approach. In the present study, we evaluated modulatory effects of ambroxol hydrochloride on quartz-induced lung inflammation in F344 rats...
April 2017: Journal of Toxicologic Pathology
https://www.readbyqxmd.com/read/28458133/scutellarin-derivatives-as-apoptosis-inducers-design-synthesis-and-biological-evaluation
#17
Tong Han, Jia Li, Jingjing Xue, He Li, Fanxing Xu, Keguang Cheng, Dahong Li, Zhanlin Li, Ming Gao, Huiming Hua
To explore novel antitumor agents with high efficiency and low toxicity, a series of NO-donating scutellarin derivatives (14-17) were synthesized and the antiproliferative activities against MCF-7, HCT-116, PC-3 and HepG2 cancer cell lines were assessed. Among them, compound 14b was the strongest with IC50 values of 2.96 μM, 7.25 μM, 0.09 μM and 0.50 μM, respectively, and displayed low toxicity against normal human liver L-O2 cells with an IC50 of 47.96 μM, showing good selectivity between normal and malignant liver cells...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28455219/ph-sensitive-polymeric-nanoparticles-for-co-delivery-of-doxorubicin-and-curcumin-to-treat-cancer-via-enhanced-pro-apoptotic-and-anti-angiogenic-activities
#18
Jinming Zhang, Jingjing Li, Zhi Shi, Yang Yang, Xi Xie, Simon MingYuen Lee, Yitao Wang, Kam W Leong, Meiwan Chen
Co-delivery of multiple drugs with complementary anticancer mechanisms by nano-carriers offers an effective strategy to treat cancer. The combination of drugs with pro-apoptotic and anti-angiogenic activities is potentially effective in treating human hepatocellular carcinoma (HCC). Herein, we developed a co-delivery system for doxorubicin (Dox), a pro-apoptotic drug, and curcumin (Cur), a potent drug for antiangiogenesis, in pH-sensitive nanoparticles (NPs) constituted with amphiphilic poly(β-amino ester) copolymer...
April 25, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28454919/new-amino-acid-schiff-base-derived-from-s-allyl-cysteine-and-methionine-alleviates-carbon-tetrachloride-induced-liver-dysfunction
#19
Periyasamy Ratha, Loganathan Chitra, Ancy Iruthayaraj, Poomani Kumaradhas, Thayumanavan Palvannan
In spite of the tremendous stride in modern medicine, conventional drugs used in the hepatotoxic management are mostly inadequate. The present study aims in the synthesis of novel Schiff base compound derived using s-ally cystiene and methionine. The newly synthesized compound, 2-((2-((2-(allylthio)-1-carboxyethyl)imino)ethylidene)amino)-4-(methylthio)butanoic acid (ACEMB) was characterized using UV-visible spectrophotometer, FTIR, (1)HNMR, and GC-MS. ACEMB showed potent in vitro antioxidant property. Chronic administration of ACEMB prior to CCl4 intoxication: i) attenuated the leakage of liver injury markers, such as, enzymes (AST, ALT, GGT, ALP and LDH) and biomolecules (bilirubin) into the blood circulation; ii) normalized the concentration of total proteins, albumin and globulin to control level; and iii) protected the liver against dyslipidemia...
April 25, 2017: Biochimie
https://www.readbyqxmd.com/read/28452736/-action-of-l-carnitine-corvitin-and-their-combination-on-functional-state-of-liver-in-experimental-model-of-reye-syndrome-in-rats
#20
M Ghonghadze, N Antelava, K Liluashvili, M Okujava, K Pachkoria
Administration of Aacetylsalicylic acid in children with viral infections (influence B, chickenpox) can be related with development of Reye syndrome - severe encephalopathy and liver insufficiency with mortality in 50% of cases. During Reye syndrome most important is deficiency of carnitine and hepatocyte damage. Decreased amount of carnitine impairs the energy function of mitochondria and gluconeogenesis as well as production of urea. As a result develops toxic encephalopathy and liver insufficiency. The goal of the research was assessment of efficacy of L-Carnitine, Corvitin and their combination on functional state of liver in experimental model of Reye Syndrome in rats...
February 2017: Georgian Medical News
keyword
keyword
119366
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"