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drug induced liver toxicity

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https://www.readbyqxmd.com/read/29344254/inhibitory-effect-of-the-low-toxic-exogenous-aryl-hydrocarbon-receptor-modulator-3-3-diindolylmethane-on-gastric-cancer-in-mice
#1
Mingli Su, Chenchen Qian, Yumin Hu, Wenhua Lu, Rongkang Huang, Minhu Chen, Jie Chen
3'3-Diindolylmethane (DIM) has been proved to exhibit anticancer properties in many solid tumors. In our previous study, we demonstrated that DIM inhibited SGC7901 cell proliferation by inducing apoptosis and delaying cell cycle progression. Herein, we further explored the anti-tumor effect of DIM on SGC-7901 tumor bearing mice. Tumors were excised, weighed, and tested by western blot and TdT-UTP nick-end labeling (TUNEL) assay. Blood samples were collected for biochemical analysis. The expression levels of AhR and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) protein were evaluated by western-blot assay...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29339102/spirulina-ameliorates-methotrexate-hepatotoxicity-via-antioxidant-immune-stimulation-and-proinflammatory-cytokines-and-apoptotic-proteins-modulation
#2
Asmaa F Khafaga, Yasser S El-Sayed
AIMS: Methotrexate (MTX) is an efficient cytotoxic drug used against various carcinogenic, inflammatory and autoimmune diseases; however, the hepatotoxicity of MTX limits its use. Therefore, the present study aimed to evaluate the potential hepatoprotective and immune-stimulant effect of Spirulina platensis (SP) against MTX acute toxicity. MAIN METHODS: Thirty-two male Wistar rats were randomly allocated into the following four groups (n = 8): control, MTX (20 mg/kg bwt, single ip injection), SP (500 mg/kg bwt, oral gavage daily for 21 days), and MTX+SP...
January 12, 2018: Life Sciences
https://www.readbyqxmd.com/read/29337684/hepatotoxicity-associated-with-statins
#3
Bensu Karahalil, Emine Hare, Göksel Koç, İrem Uslu, Kerem Şentürk, Yağmur Özkan
Treatment with statins is known all over the world. They are generally considered safe at therapeutic doses. Nevertheless, clinical trials are not enough to assess their scarce adverse effects such as idiosyncratic drug induced liver injury (DILI). Due to some conditions, such as concomitant usage (drug-drug interaction using an identical metabolising enzyme) and genetic polymorphisms, there is an increasing concern about their safety. Hepatotoxicity and rhabdomyolysis have begun to appear in published studies...
December 20, 2017: Arhiv za Higijenu Rada i Toksikologiju
https://www.readbyqxmd.com/read/29329425/comparison-of-hepatic-2d-sandwich-cultures-and-3d-spheroids-for-long-term-toxicity-applications-a-multi-center-study
#4
Catherine C Bell, Anita C A Dankers, Volker M Lauschke, Rowena Sison-Young, Roz Jenkins, Cliff Rowe, Chris Goldring, Kevin Park, Sophie Regan, Tracy Walker, Chris Schofield, Audrey Baze, Alison J Foster, Dominic Williams, Amy W M van de Ven, Frank Jacobs, Jos van Houdt, Tuula Lähteenmäki, Jan Snoeys, Satu Juhila, Lysiane Richert, Magnus Ingelman-Sundberg
Primary human hepatocytes (PHH) are commonly used for in vitro studies of drug-induced liver injury. However, when cultured as 2D monolayers, PHH lose crucial hepatic functions within hours. This dedifferentiation can be ameliorated when PHH are cultured in sandwich configuration (2Dsw), particularly when cultures are regularly re-overlaid with extracellular matrix, or as 3D spheroids. In this study, the six participating laboratories evaluated the robustness of these two model systems made from cryopreserved PHH from the same donors considering both inter-donor and inter-lab variability and compared their suitability for use in repeated-dose toxicity studies using 5 different hepatotoxins with different toxicity mechanisms...
January 10, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29319822/an-animal-model-of-abacavir-induced-hla-mediated-liver-injury
#5
Binbin Song, Shigeki Aoki, Cong Liu, Takeshi Susukida, Kousei Ito
Genome-wide association studies indicate that several idiosyncratic adverse drug reactions are highly associated with specific human leukocyte antigen (HLA) alleles. For instance, abacavir, a human immunodeficiency virus reverse transcriptase inhibitor, induces multi-organ toxicity exclusively in patients carrying the HLA-B*57:01 allele. However, the underlying mechanism is unclear due to a lack of appropriate animal models. Previously, we developed HLA-B*57:01 transgenic mice and found that topical application of abacavir to the ears induced proliferation of CD8+ lymphocytes in local lymph nodes...
January 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29316113/drug-induced-liver-injury-is-frequently-associated-with-severe-cutaneous-adverse-drug-reactions-experience-from-two-australian-tertiary-hospitals
#6
Wendy C Fang, Nikki R Adler, Linda V Graudins, Caitlin Goldblatt, Michelle Sy Goh, Stuart K Roberts, Jason A Trubiano, Ar Kar Aung
BACKGROUND: Drug-induced liver injury can be associated with certain cutaneous adverse drug reactions. AIMS: We aim to demonstrate the prevalence of drug-induced liver injury in patients with cutaneous adverse drug reactions. Severity and patterns of liver injury, risk factors, causal medications and outcomes are also examined. METHODS: A retrospective cohort study of patients with cutaneous adverse drug reactions was conducted across two hospitals in Australia...
January 8, 2018: Internal Medicine Journal
https://www.readbyqxmd.com/read/29312593/shikonin-induces-ros-based-mitochondria-mediated-apoptosis-in-colon-cancer
#7
Wenquan Liang, Jianxin Cui, Kecheng Zhang, Hongqing Xi, Aizhen Cai, Jiyang Li, Yunhe Gao, Chong Hu, Yi Liu, Yixun Lu, Ning Wang, Xiaosong Wu, Bo Wei, Lin Chen
Colon cancer is the third most common malignancy worldwide, and chemotherapy is a widely used strategy in clinical therapy. Chemotherapy-resistant of colon cancer is the main cause of recurrence and progression. Novel drugs with efficacy and safety in treating colon cancer are urgently needed. Shikonin, a naphthoquinone derived from the roots of the herbal plant Lithospermum erythrorhizon, has been determined to be a potent anti-tumor agent. The aim of the present study was to detect the underlying anti-tumor mechanism of shikonin in colon cancer...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29291400/liver-organ-on-a-chip
#8
REVIEW
Colin H Beckwitt, Amanda M Clark, Sarah Wheeler, D Lansing Taylor, Donna B Stolz, Linda Griffith, Alan Wells
The liver plays critical roles in both homeostasis and pathology. It is the major site of drug metabolism in the body and, as such, a common target for drug-induced toxicity and is susceptible to a wide range of diseases. In contrast to other solid organs, the liver possesses the unique ability to regenerate. The physiological importance and plasticity of this organ make it a crucial system of study to better understand human physiology, disease, and response to exogenous compounds. The purpose of this review is to inform the reader of the significance and available methods for replicating human liver physiology and pathology ex vivo...
December 29, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29285401/multifunctional-stimuli-responsive-polymer-gated-iron-and-gold-embedded-silica-nano-golf-balls-nanoshuttles-for-targeted-on-demand-theranostics
#9
Liping Wang, Grace Jang, Deependra Kumar Ban, Vrinda Sant, Jay Seth, Sami Kazmi, Nirav Patel, Qingqing Yang, Joon Lee, Woraphong Janetanakit, Shanshan Wang, Brian P Head, Gennadi Glinsky, Ratneshwar Lal
Multi-functional nanoshuttles for remotely targeted and on-demand delivery of therapeutic molecules and imaging to defined tissues and organs hold great potentials in personalized medicine, including precise early diagnosis, efficient prevention and therapy without toxicity. Yet, in spite of 25 years of research, there are still no such shuttles available. To this end, we have designed magnetic and gold nanoparticles (NP)-embedded silica nanoshuttles (MGNSs) with nanopores on their surface. Fluorescently labeled Doxorubicin (DOX), a cancer drug, was loaded in the MGNSs as a payload...
2017: Bone Research
https://www.readbyqxmd.com/read/29279717/the-evaluation-of-toxicity-induced-by-psoraleae-fructus-in-rats-using-untargeted-metabonomic-method-based-on-uplc-q-tof-ms
#10
Yanyan Xu, Yiwei Zhao, Jiabin Xie, Xue Sheng, Yubo Li, Yanjun Zhang
Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29277777/amifostine-protects-mouse-liver-against-radiation-induced-autophagy-blockage
#11
Michael I Koukourakis, Alexandra Giatromanolaki, Konstantina Fylaktakidou, Maria Kouroupi, Efthimios Sivridis, Christos E Zois, Dimitra Kalamida, Achilleas Mitrakas, Stamatia Pouliliou, Ilias V Karagounis, Konstantinos Simopoulos, David J P Ferguson, Adrian L Harris
BACKGROUND/AIM: Amifostine is the only selective normal tissue cytoprotector, approved for the protection against platinum toxicities and radiotherapy-induced xerostomia. Free radical scavenger and DNA repair activities have been attributed to the drug. MATERIALS AND METHODS: We investigated the effect of amifostine on autophagy, lysosomal biogenesis and lipophagy of normal mouse liver exposed to clinically relevant doses of radiation. RESULTS: The study provides evidence that ionizing radiation blocks autophagy activity and lysosomal biogenesis in normal mouse liver...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29248475/alleviating-the-hepatotoxicity-of-trazodone-via-supramolecular-encapsulation
#12
Qiaoxian Huang, Shengke Li, Hang Yin, Chunming Wang, Simon M Y Lee, Ruibing Wang
In order to develop a novel strategy to alleviate the inherent hepatotoxicity of antidepressant trazodone (TZ), Cucurbit[7]uril (CB[7]) was adopted as pharmaceutical excipients and was studied for its capability to reduce the hepatotoxicity of TZ via supramolecular encapsulation. CB[7] was found to form strong 1:1 host-guest complexes with TZ and its metabolite m-chlorophenyl piperazine (mCPP), with binding constants of 1.50 (±0.13) × 106 M-1 and 6.90 (±0.49) × 105 M-1, respectively. The supramolecular complexations were examined by 1H NMR and UV-visible spectroscopic titrations, ESI-MS and ITC...
December 14, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29247884/a-low-toxicity-dna-alkylating-n-mustard-quinoline-conjugate-with-preferential-sequence-specificity-exerts-potent-antitumor-activity-against-colorectal-cancer
#13
Tai-Lin Chen, Yi-Wen Lin, Yan-Bo Chen, Jing-Jer Lin, Tsann-Long Su, Chia-Ning Shen, Te-Chang Lee
Efficacy and safety are fundamental prerequisites for anticancer drug development. In the present study, we explored the anti-colorectal cancer (CRC) activity of SL-1, a DNA-directed N-mustard-quinoline conjugate. The N-mustard moiety in SL-1 induced DNA strand breaks, interstrand cross-links (ICLs), G2/M arrest, and apoptosis, whereas its quinoline moiety preferentially directed SL-1 to target the selective guanine sequence 5'-G-G/C-N-G-C/T-3'. Notably, SL-1 was highly cytotoxic to various CRC cell lines. Experiments using xenograft models revealed that SL-1 was more potent than 5-fluorouracil (5-FU) and oxaliplatin for suppressing the growth of RKO and RKO-E6 (oxaliplatin-resistant subline) cells as well as metastatic SW620 cells...
December 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29245301/copper-associated-hepatitis-in-a-patient-with-chronic-myeloid-leukemia-following-hematopoietic-stem-cell-transplantation-a-case-report
#14
Ching-Fen Lee, Chi-Hua Chen, Yu-Chuan Wen, Tsung-Yen Chang, Ming-Wei Lai, Tang-Her Jaing
RATIONALE: We report a complicated case of cholestatic hepatitis with suspected autoimmune hemolytic anemia (AIHA) and copper toxicity syndrome after HSCT and donor lymphocyte infusion (DLI). PATIENT CONCERNS: A 19-year-1-month-old girl presented with a history of CML. She underwent matched unrelated donor HSCT and donor lymphocyte infusion subsequently. Three months later, yellowish discoloration of the skin was found, which was accompanied by progressive itchy skin, easy fatigability, insomnia, and dark urine output...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29229971/development-of-decision-forest-models-for-prediction-of-drug-induced-liver-injury-in-humans-using-a-large-set-of-fda-approved-drugs
#15
Huixiao Hong, Shraddha Thakkar, Minjun Chen, Weida Tong
Drug-induced liver injury (DILI) presents a significant challenge to drug development and regulatory science. The FDA's Liver Toxicity Knowledge Base (LTKB) evaluated >1000 drugs for their likelihood of causing DILI in humans, of which >700 drugs were classified into three categories (most-DILI, less-DILI, and no-DILI). Based on this dataset, we developed and compared 2-class and 3-class DILI prediction models using the machine learning algorithm of Decision Forest (DF) with Mold2 structural descriptors...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222033/multiple-perspectives-of-qingkailing-injection-fraction-single-compound-in-revealing-the-hepatotoxicity-of-baicalin-and-hyodeoxycholic-acid
#16
Jiayu Zhang, Shifeng Wang, Lulu Xu, Qiao Zhang, Zhanpeng Shang, Yanling Zhang, Qinghua Wu, Shiyou Li, Yanjiang Qiao
ETHNOPHARMACOLOGICAL RELEVANCE: The complexity of ingredients in traditional Chinese medical formulas and the limited consideration of toxicological responses are fundamental issues that hamper prognostic information of drug quality control. MATERIALS AND METHODS: A multidisciplinary approach for quality control of Qingkailing injection (QKL) regarding drug induced liver toxicity was described for the first time. High content image analysis (HCA) was combined with reverse-phase chromatographic separation and high-resolution MS detection technologies to provide the dynamic responses of HepG2 cell injury...
December 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29217891/trimethoprim-sulfamethoxazole-induced-hepatotoxicity-in-a-renal-transplant-patient
#17
R Slim, N Asmar, C Yaghi, K Honein, R Sayegh, D Chelala
Drug-induced liver injury (DILI) represents liver damage from various therapeutic drugs. Antimicrobials are among the most common causes of DILI. We report a case of hepatic toxicity due to Trimethoprim-sulfamethoxazole (TMP-SMX) in a patient who underwent renal transplantation. Diagnosis has been made after a careful history taking, exclusion of competing etiologies and reversal of biochemical abnormalities after withdrawal of the antibiotic. TMP-SMX liver toxicity is well known but remains unpredictable and is rarely reported...
November 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/29210687/identification-and-risk-assessment-of-human-and-veterinary-antibiotics-in-the-wastewater-treatment-plants-and-the-adjacent-sea-in-tunisia
#18
Leyla Tahrani, Joris Van Loco, Roel Anthonissen, Luc Verschaeve, Hedi Ben Mansour, Tim Reyns
In the following study, we came up with and validated a prompt, sensitive and precise method for the simultaneous determination of 56 antimicrobial drugs (tetracyclines, sulfonamides, β-lactams, macrolides and quinolones) using the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). This method was implemented with success to determine antibiotics in samples collected from four wastewater treatment plants and five coasts in Tunisia. Results showed the presence of high concentrations of antibiotics that ranged from 0...
December 2017: Water Science and Technology: a Journal of the International Association on Water Pollution Research
https://www.readbyqxmd.com/read/29209210/critical-role-of-hepatic-cyp450s-in-the-testis-specific-toxicity-of-5r-5-hydroxytriptolide-in-c57bl-6-mice
#19
Cunzhi Yu, Yu Li, Mingxia Liu, Man Gao, Chenggang Li, Hong Yan, Chunzhu Li, Lihan Sun, Liying Mo, Chunyong Wu, Xinming Qi, Jin Ren
Low solubility, tissue accumulation, and toxicity are chief obstacles to developing triptolide derivatives, so a better understanding of the pharmacokinetics and toxicity of triptolide derivatives will help with these limitations. To address this, we studied pharmacokinetics and toxicity of (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative immunosuppressant in a conditional knockout (KO) mouse model with liver-specific deletion of CYP450 reductase. Compared to wild type (WT) mice, after LLDT-8 treatment, KO mice suffered severe testicular toxicity (decreased testicular weight, spermatocytes apoptosis) unlike WT mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29204817/oxyphenbutazone-promotes-cytotoxicity-in-rats-and-hep3b-cellsvia-suppression-of-pge2-and-deactivation-of-wnt-%C3%AE-catenin-signaling-pathway
#20
Shakir Saleem, Ruqaiyah Khan, Muhammad Afzal, Imran Kazmi
Hepatocellular carcinoma (HCC) is the fifth leading cause of death and is generally typified by elevated liver enzyme biomarkers, antioxidants, and chronic inflammation of hepatocytes. Although currently available drugs have shown remarkable alleviation of the cancerous condition, but at the same time they present a more severe challenge of toxic effects due to chemotherapy. Therefore, in order to bring more patient-compliant therapy, we aimed to refurbish the use of a COX inhibitor, oxyphenbutazone (OPB), with low dose of methotrexate (MTX) to treat diethyl nitrosamine (DENA)-induced HCC in Wistar rats and in Hep3B cells...
December 4, 2017: Molecular and Cellular Biochemistry
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