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https://www.readbyqxmd.com/read/28214631/discovery-of-quinone-directed-antitumor-agents-selectively-bioactivated-by-nqo1-over-cpr-with-improved-safety-profile
#1
Jinlei Bian, Xiang Li, Nan Wang, Xingsen Wu, Qidong You, Xiaojin Zhang
In this work, we mainly focused on discovering compounds with good selectivity for NQO1 over CPR. The NQO1-mediated two-electron reduction of compounds would kill cancer cells selectively, while CPR-mediated one-electron reduction would induce potential hepatotoxicity. Several novel quinone-directed antitumor agents were discovered as specific NQO1 substrates through structure-activity relationship studies. Among them, compound 3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione (12b) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by CPR...
February 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28214545/potential-of-amphiphilic-graft-copolymer-%C3%AE-tocopherol-succinate-g-carboxymethyl-chitosan-in-modulating-the-permeability-and-anticancer-efficacy-of-tamoxifen
#2
Sunil K Jena, Sanjaya K Samal, Shamandeep Kaur, Mahesh Chand, Abhay T Sangamwar
Recent studies showed an enhanced oral bioavailability of tamoxifen (TMX) by hydrophobically modified α-tocopherol succinate-g-carboxymethyl chitosan (Cmc-TS) micelles. As a continued effort, here we evaluated TMX-loaded polymeric micelles (TMX-PMs) for its enhanced permeability with increased anticancer efficacy and decreased hepatotoxicity. We employed co-solvent evaporation technique to encapsulate TMX into Cmc-TS. Apparent permeability assay of TMX-PMs was performed on Caco-2 cell line. The absorptive transport of TMX increased significantly about 3...
February 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28214329/-p-clphse-2-reduces-hepatotoxicity-induced-by-monosodium-glutamate-by-improving-mitochondrial-function-in-rats
#3
Caroline B Quines, Pietro M Chagas, Diane Hartmann, Nélson R Carvalho, Félix A Soares, Cristina W Nogueira
It is has been demonstrated that mitochondrial dysfunction, oxidative stress and chronic inflammatory process are associated with progress of morbid obesity in human patients. For this reason, the searching for safe and effective antiobesity drugs has been the subject of intense research. In this context, the organic selenium compounds have attracted much attention due to their pharmacological properties, such as antihyperglycemic, antioxidant and anti-inflammatory. The aim of this study was to evaluate the hepatoprotective action of p-chloro-diphenyl diselenide (p-ClPhSe)2 , an organic selenium compound, in a model of obesity induced by monosodium glutamate (MSG) administration in rats...
February 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28214085/folic-acid-protects-against-lead-acetate-induced-hepatotoxicity-by-decreasing-nf-%C3%AE%C2%BAb-il-1%C3%AE-production-and-lipid-peroxidation-mediataed-cell-injury
#4
Eman S H Abd Allah, Dalia M Badary
Folic acid plays an important role in cellular metabolic activities. The present study was designed to investigate the protective effect of folic acid against lead acetate-induced hepatotoxicity. Twenty four male Wistar albino rats were randomly divided into four groups, six animals each. Negative control group received the vehicle, positive control group received 1mg/kg folic acid for five consecutive days/week for 4 weeks orally, lead-exposed group received 10mg/kg lead acetate intraperitoneally (IP) for five consecutive days/week for 4 weeks, and lead-treated group received 10mg/kg lead acetate IP and 1mg/kg folic acid orally for five consecutive days/week for 4 weeks concurrently...
February 10, 2017: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/28213093/enhanced-effect-of-geldanamycin-nanocomposite-against-breast-cancer-cells-growing-in-vitro-and-as-xenograft-with-vanquished-normal-cell-toxicity
#5
Suma Prabhu, Preeta Ananthanarayanan, Kannangar Aziz Sajida, Sharada Rai, Srinivas Mutalik, Satish Rao Bola Sadashiva
Despite enormous advances in remedies developed for breast cancer, an effective therapeutic strategy by targeting malignant cells with the least normal tissue toxicity is yet to be developed. Hsp90 is considered to be an important therapeutic target to inhibit cell proliferation. Geldanamycin (GDM), a potent inhibitor of Hsp90 was withdrawn from clinical trials due to its undesirable hepatotoxicity. We report a superparamagnetic iron oxide (SPION) based polymeric nanocomposite of GDM augmenting anticancer competence with decreased hepatic toxicity...
February 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28213091/convergence-of-hepcidin-deficiency-systemic-iron-overloading-heme-accumulation-and-rev-erb%C3%AE-%C3%AE-activation-in-aryl-hydrocarbon-receptor-elicited-hepatotoxicity
#6
Kelly A Fader, Rance Nault, Mathew P Kirby, Gena Markous, Jason Matthews, Timothy R Zacharewski
Persistent aryl hydrocarbon receptor (AhR) agonists elicit dose-dependent hepatic lipid accumulation, oxidative stress, inflammation, and fibrosis in mice. Iron (Fe) promotes AhR-mediated oxidative stress by catalyzing reactive oxygen species (ROS) production. To further characterize the role of Fe in AhR-mediated hepatotoxicity, male C57BL/6 mice were orally gavaged with sesame oil vehicle or 0.01-30μg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) every 4days for 28days. Duodenal epithelial and hepatic RNA-Seq data were integrated with hepatic AhR ChIP-Seq, capillary electrophoresis protein measurements, and clinical chemistry analyses...
February 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28210952/two-dechlorinated-chlordecone-derivatives-formed-by-in-situ-chemical-reduction-are-devoid-of-genotoxicity-and-mutagenicity-and-have-lower-proangiogenic-properties-compared-to-the-parent-compound
#7
Samuel Legeay, Pierre-André Billat, Nicolas Clere, Fabrice Nesslany, Sébastien Bristeau, Sébastien Faure, Christophe Mouvet
Chlordecone (CLD) is a chlorinated hydrocarbon insecticide, now classified as a persistent organic pollutant. Several studies have previously reported that chronic exposure to CLD leads to hepatotoxicity, neurotoxicity, raises early child development and pregnancy complications, and increases the risk of liver and prostate cancer. In situ chemical reduction (ISCR) has been identified as a possible way for the remediation of soils contaminated by CLD. In the present study, the objectives were (i) to evaluate the genotoxicity and the mutagenicity of two CLD metabolites formed by ISCR, CLD-5a-hydro, or CLD-5-hydro (5a- or 5- according to CAS nomenclature; CLD-1Cl) and tri-hydroCLD (CLD-3Cl), and (ii) to explore the angiogenic properties of these molecules...
February 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28209603/deoxyribonuclease-partially-ameliorates-thioacetamide-induced-hepatorenal-injury
#8
Lenka Vokálová, Lucia Lauková, Jozef Čonka, Veronika Melišková, Veronika Borbélyová, Janka Bábíčková, Ľubomíra Tóthová, Július Hodosy, Barbora Vlková, Peter Celec
Several recent studies have shown that liver injury is associated with the release of DNA from hepatocytes. This DNA stimulates innate immunity and induces sterile inflammation exacerbating the liver damage. Similar mechanisms have been described for acute renal injury. Deoxyribonuclease degrades cell-free DNA and can potentially prevent some of the induced tissue damage. In this study the effects of thioacetamide-induced hepatorenal injury on plasma DNA in rats were analysed. Plasma DNA of both nuclear and mitochondrial origin was higher in thioacetamide-treated animals...
February 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28209108/acute-temozolomide-induced-liver-injury%C3%A2-mixed-type-hepatocellular-and-cholestatic-toxicity
#9
C Aygun, A Y Altınok, A Çakır, A F Agan, Y Balaban
Temozolomide (TMZ) is an oral imidazotetrazine methylating agent which is used for the treatment of glioblastoma multiforme (GBM). We report a case of acute hepatotoxicity in a 53-year old male patient after administration of TMZ for GBM. He had fatigue, nausea, anorexia and jaundice. His laboratory analysis showed alanine aminotransferase(ALT) : 632 IU/L (normal range 0-40) ; aspartate aminotransferase(AST) : 554 IU/L (normal range 5-34) ; alkaline phosphatase(ALP) : 1143 IU/L (normal range 40-150) ; γ-glutamyl transpeptidase(GGT) : 514 IU/L (normal range 9-64 IU/L) ; total bilirubin : 15...
September 2016: Acta Gastro-enterologica Belgica
https://www.readbyqxmd.com/read/28208716/cell-imaging-counting-as-a-novel-ex-vivo-approach-for-investigating-drug-induced-hepatotoxicity-in-zebrafish-larvae
#10
Xuan-Bac Nguyen, Stanislav Kislyuk, Duc-Hung Pham, Angela Kecskés, Jan Maes, Deirdre Cabooter, Pieter Annaert, Peter De Witte, Annelii Ny
Drug-induced liver injury (DILI) is the most common reason for failures during the drug development process and for safety-related withdrawal of drugs from the pharmaceutical market. Therefore, having tools and techniques that can detect hepatotoxic properties in drug candidates at an early discovery stage is highly desirable. In this study, cell imaging counting was used to measure in a fast, straightforward, and unbiased way the effect of paracetamol and tetracycline, (compounds known to cause hepatotoxicity in humans) on the amount of DsRed-labeled hepatocytes recovered by protease digestion from Tg(fabp10a:DsRed) transgenic zebrafish...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208250/simultaneous-voltammetric-determination-of-acetaminophen-and-isoniazid-hepatotoxicity-related-drugs-utilizing-bismuth-oxide-nanorod-modified-screen-printed-electrochemical-sensing-platforms
#11
Bahaa G Mahmoud, Mohamed Khairy, Farouk A Rashwan, Craig E Banks
To overcome the recent outbreaks of hepatotoxicity-related drugs, a new analytical tool for the continuously determination of these drugs in human fluids is required. Electrochemical-based analytical methods offer an effective, rapid, and simple tool for on-site determination of various organic and inorganic species. However, the design of a sensitive, selective, stable, and reproducible sensor is still a major challenge. In the present manuscript, a facile, one-pot hydrothermal synthesis of bismuth oxide (Bi2O2...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28207511/autoimmune-hepatitis-in-patients-with-human-immunodeficiency-virus-hiv-case-reports-of-a-rare-but-important-diagnosis-with-therapeutic-implications
#12
Leila Kia, Adam Beattie, Richard M Green
RATIONALE: Chronic liver disease is a major cause of morbidity and mortality in patients with HIV. However, autoimmune hepatitis (AIH) in patients with HIV has rarely been reported. Our aim was to evaluate a cohort of patients with HIV and AIH and identify clinical presentations and outcomes. PATIENT CONCERNS: Management of autoimmune hepatitis in context of human immunodeficiency virus, long-term outcomes, and safety in setting of underlying immunocompromised state...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28207423/an-unusual-case-of-nitrofurantoin-associated-hepatotoxicity
#13
Poornima Ramadas, Prathik Krishnan, Vincent Frechette
No abstract text is available yet for this article.
February 15, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28205314/comparison-of-lc-ms-ms-vs-chemiluminescent-microparticle-immunoassay-in-measuring-the-valproic-acid-concentration-in-plasma-of-epilepsy-patients-in-a-new-perspective
#14
Zhipeng Wang, Yunlei Yun, Xinfang Xie, Chunhua You, Haijun Miao, Feng Zhang, Shouhong Gao, Wansheng Chen
OBJECTIVES: This study was designed to compare the performance of LC-MS/MS with chemiluminescent microparticle immunoassay (CMIA) for determination of VPA in epilepsy patients in the perspective of metabolites' hepatotoxicity. METHOD: Samples were collected and then analyzed using both LC-MS/MS and CMIA. A LO2 cells (normal human hepatic cells) experiment was carried out to confirm VPA metabolites' hepatotoxicity using AST(Aspertate Aminotransferase, AST), ALT(Alanine aminotransferase, ALT) and LDH(lactate dehydrogenase, LDH) in supernate as index...
February 15, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28205080/assessment-of-cu-zn-edta-parenteral-toxicity-in-calves
#15
Luis Emilio Fazzio, Diana Esther Rosa, Sebastian Julio Picco, Guillermo Alberto Mattioli
Copper (Cu) parenteral administration is used in a beef cow-calf operations to prevent or correct Cu deficiency in bovines. At present, Zinc (Zn) salts have been incorporated to complement Cu antioxidant effect. A risk of hepatotoxicity generated by overdose is a negative consequence of injectable Cu application. Cu-Zn EDTA appears as an alternative; however, data about its toxicity is unknown. The aim of this study was to assess toxicity risk of different doses of Cu-Zn EDTA in calves. Thirty two Aberdeen Angus calves of 162 (±20) kg BW were assigned to 4 groups (n = 8), homogeneous in weight, sex, and age...
February 15, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28203134/black-cohosh-hepatotoxicity-with-autoimmune-hepatitis-presentation
#16
Diana L Franco, Santosh Kale, Dora M Lam-Himlin, M Edwyn Harrison
Herbal medicines have been used for the treatment of various ailments since time immemorial. Black cohosh (BC) is well known for the treatment of postmenopausal symptoms, with conflicting evidence supporting its safety and benefits. We present a rare case of BC-induced autoimmune hepatitis (AIH) with hepatotoxicity in a 69-year-old female. To our knowledge, this represents the third case of BC-induced AIH.
January 2017: Case Reports in Gastroenterology
https://www.readbyqxmd.com/read/28198914/action-of-vitamin-e-on-experimental-severe-acute-liver-failure
#17
Fabiano Moraes Miguel, Elizângela Gonçalves Schemitt, Josieli Raskopf Colares, Renata Minuzzo Hartmann, Maria Isabel Morgan-Martins, Norma Possa Marroni
BACKGROUND: Severe Acute Liver Failure (ALF) is a life-threatening clinical syndrome characterized by hepatocyte necrosis, loss of hepatic architecture, and impairment of liver functions. One of the main causes of ALF is hepatotoxicity from chemical agents, which damage hepatocytes and result in increase of reactive oxygen species. The vitamin E isoform is the one with the strongest biological antioxidant activity. OBJECTIVE: To evaluate the antioxidant effect of vitamin E in this ALF model...
February 13, 2017: Arquivos de Gastroenterologia
https://www.readbyqxmd.com/read/28196650/protective-role-of-p53-in-acetaminophen-hepatotoxicity
#18
Yazhen Huo, Shutao Yin, Mingzhu Yan, Sanda Win, Tin Aung Than, Mariam Aghajan, Hongbo Hu, Neil Kaplowitz
p53 is a tumor suppressor with a pro-death role in many conditions. However, in some contexts, evidence supports a pro-survival function. p53 has been shown to be activated in acetaminophen (APAP) toxicity but the impact of this on toxicity is uncertain. In the present study, we have found that p53 plays a protective role in APAP-induced liver injury. We inhibited p53 using three different approaches in mice, pifithrin-α (PFTα), knockdown of p53 expression with antisense oligonucleotide, and p53 knockout...
February 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28196344/identification-characterization-and-in-silico-admet-prediction-of-roflumilast-degradation-products
#19
Mariana S Pinheiro, Gil M Viana, Bárbara de A Abrahim Vieira, Alessandra Mendonça Teles de Souza, Carlos Rangel Rodrigues, Rita de Cássia E E Marins, Lúcio M Cabral, Valéria P de Sousa
The present study reports the degradation behavior of roflumilast (RFL), a new drug developed for the treatment of chronic obstructive pulmonary disease. The degradation of RFL was tested under various stress conditions as per the guidelines of the International Conference on Harmonization. The degradation products (DPs) of RFL were identified, characterized and in silico predictions were made of their pharmacokinetic properties, absorption, distribution, metabolism, excretion and toxicity (ADMET). RFL was subjected to various stress conditions including photodegradation, alkaline and acidic hydrolysis, oxidative and metallic degradation...
February 6, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28196310/gemcitabine-cisplatin-versus-gemcitabine-oxaliplatin-doublet-chemotherapy-in-advanced-gallbladder-cancers-a-match-pair-analysis
#20
Anant Ramaswamy, Vikas Ostwal, Rakesh Pinniti, Sadhana Kannan, Prabhat Bhargava, Chaitali Nashikkar, Jimmy Mirani, Shripad Banavali
BACKGROUND: Gemcitabine-cisplatin (GC) and gemcitabine-oxaliplatin (GO) are the most commonly used regimens in advanced gallbladder cancer (GBC). METHODS: The data of patients with advanced GBC, treated between January 2013 and June 2015 were retrieved. A 1:1 matching without replacement was performed by using nearest neighbour matching method. RESULTS: 326 patients (163 GC and 163 GO), were matched 1:1 by age and gender. The response rates for GC and GO were 31...
February 14, 2017: Journal of Hepato-biliary-pancreatic Sciences
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