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https://www.readbyqxmd.com/read/28335386/revisiting-the-metabolism-and-bioactivation-of-ketoconazole-in-human-and-mouse-using-liquid-chromatography-mass-spectrometry-based-metabolomics
#1
Ju-Hyun Kim, Won-Gu Choi, Sangkyu Lee, Hye Suk Lee
Although ketoconazole (KCZ) has been used worldwide for 30 years, its metabolic characteristics are poorly described. Moreover, the hepatotoxicity of KCZ limits its therapeutic use. In this study, we used liquid chromatography-mass spectrometry-based metabolomics to evaluate the metabolic profile of KCZ in mouse and human and identify the mechanisms underlying its hepatotoxicity. A total of 28 metabolites of KCZ, 11 of which were novel, were identified in this study. Newly identified metabolites were classified into three categories according to the metabolic positions of a piperazine ring, imidazole ring, and N-acetyl moiety...
March 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28334048/hepatoprotective-effect-of-sitagliptin-against-methotrexate-induced-liver-toxicity
#2
Hany M Abo-Haded, Mohamed A Elkablawy, Zeyad Al-Johani, Osama Al-Ahmadi, Dina S El-Agamy
Sitagliptin is selective dipeptidyl peptidase-4 inhibitor (DPP4-I), used clinically as a new oral anti-diabetic agent. This study explored the underlying mechanisms of the hepatoprotective role of sitagliptin pretreatment against methotrexate (MTX) induced hepatotoxicity in mice. Forty mice were divided into four groups (10 mice each); control, MTX, and two sitagliptin groups (pretreated with sitagliptin 10 and 20 mg/kg/day, respectively) for five consecutive days prior to MTX injection. Results showed that MTX induced marked hepatic injury in the form of cloudy swelling, hydropic degeneration, apoptosis and focal necrosis in all hepatic zones...
2017: PloS One
https://www.readbyqxmd.com/read/28333080/a-review-epigenetic-mechanism-in-ochratoxin-a-toxicity-studies
#3
REVIEW
Liye Zhu, Boyang Zhang, Yaqi Dai, Hongyu Li, Wentao Xu
Ochratoxin A (OTA) is a natural contaminant that has displayed nephrotoxicity and hepatotoxicity in mammals. It contaminates a great variety of foodstuffs and threatens people's lives. The molecular mechanism of OTA-induced toxicity has been studied since 1965. Moreover, epigenetic mechanisms are also studied in OTA-induced toxicity. Additionally, the mode of OTA epigenetic research has been advanced in research hotspots. However, there is still no epigenetic study of OTA-induced toxicity. In this review, we discuss the relationship between these epigenetic mechanisms and OTA-induced toxicity...
March 23, 2017: Toxins
https://www.readbyqxmd.com/read/28333016/predictors-of-liver-toxicity-following-stereotactic-body-radiation-therapy-for-hepatocellular-carcinoma
#4
Michael Velec, Carol R Haddad, Tim Craig, Lisa Wang, Patricia Lindsay, James Brierley, Anthony Brade, Jolie Ringash, Rebecca Wong, John Kim, Laura A Dawson
PURPOSE: To identify risk factors associated with a decline in liver function after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma. METHODS AND MATERIALS: Data were analyzed from patients with hepatocellular carcinoma treated on clinical trials of 6-fraction SBRT. Liver toxicity was defined as an increase in Child-Pugh (CP) score ≥2 three months after SBRT. Clinical factors, SBRT details, and liver dose-volume histogram (DVH) parameters were tested for association with toxicity using logistic regression...
April 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28332306/impact-of-iatrogenic-iron-overload-on-the-course-of-hepatitis-c-in-dialysis-population-a-plea-for-caution
#5
Guy Rostoker, Nosratola D Vaziri
About 2.5% of the world population, corresponding to about 177 million individuals, are infected by hepatitis C virus (HCV), a small, single-stranded RNA virus. The prevalence of HCV infection among dialysis patients in Japan, Europe, and North America during the 2012 to 2015 period was found to be 8.7% in the DOPPS study. Nosocomial HCV spread in hemodialysis facilities still occurs. Increased hepatic tissue iron has been shown to play a deleterious role in the course of hepatitis C, favor development of fibrosis and cirrhosis and possibly increase the risk of liver cancer in the general population...
March 23, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28331564/effects-of-butyric-acid-and-arsenic-on-isolated-pancreatic-islets-and-liver-mitochondria-of-male-mouse
#6
Akram Ahangarpour, Ali Akbar Oroojan, Mohsen Rezae, Mohammad Javad Khodayar, Soheila Alboghobeish, Marzieh Zeinvand
AIM: The aim of the present study was to evaluate the different doses of Butyric acid (BA) and Arsenic (As) in liver mitochondria oxidative stress and pancreatic islet insulin secretion of male mouse. BACKGROUND: BA is found in many foods and As as a toxic metal is present in drinking water. They can induce oxidative stress in tissues. METHODS: In this experimental study, Liver mitochondria were isolated by administration of the different centrifugation method and pancreatic islets were isolated by collagenase method...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28331445/negligible-oval-cell-proliferation-following-ischemia-reperfusion-injury-with-and-without-partial-hepatectomy
#7
Ek Khoon Tan, Maureen Shuh, Heather Francois-Vaughan, Jennifer A Sanders, Ari J Cohen
BACKGROUND: Hepatic oval cells proliferate to replace hepatocytes and restore liver function when hepatocyte proliferation is compromised or inadequate. Exposure to chemical carcinogens, severe liver steatosis, and partial hepatectomy has been used in animal models to demonstrate the role of oval cells in liver regeneration. Ischemia-reperfusion injury (IRI) causes hepatocellular damage and death in the absence of confounding chemical toxicity; however, oval cell induction by IRI has not been demonstrated in vivo...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28331334/safety-efficacy-and-clinical-utility-of-asparaginase-in-the-treatment-of-adult-patients-with-acute-lymphoblastic-leukemia
#8
REVIEW
Jamie Koprivnikar, James McCloskey, Stefan Faderl
Adults with acute lymphoblastic leukemia (ALL) are known to have inferior outcomes compared to the pediatric population. Although the reasons for this are likely manyfold, the agents utilized and the increased intensity of pediatric treatments compared to adult treatments are likely significant contributing factors. Asparaginase, an enzyme that converts asparagine to aspartic acid, forms the backbone of almost all pediatric regimens and works by depleting extracellular asparagine, which ALL cells are unable to synthesize...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28330995/hepatic-fcrn-regulates-albumin-homeostasis-and-susceptibility-to-liver-injury
#9
Michal Pyzik, Timo Rath, Timothy T Kuo, Sanda Win, Kristi Baker, Jonathan J Hubbard, Rosa Grenha, Amit Gandhi, Thomas D Krämer, Adam R Mezo, Zachary S Taylor, Kevin McDonnell, Vicki Nienaber, Jan Terje Andersen, Atsushi Mizoguchi, Laurence Blumberg, Shalaka Purohit, Susan D Jones, Greg Christianson, Wayne I Lencer, Inger Sandlie, Neil Kaplowitz, Derry C Roopenian, Richard S Blumberg
The neonatal crystallizable fragment receptor (FcRn) is responsible for maintaining the long half-life and high levels of the two most abundant circulating proteins, albumin and IgG. In the latter case, the protective mechanism derives from FcRn binding to IgG in the weakly acidic environment contained within endosomes of hematopoietic and parenchymal cells, whereupon IgG is diverted from degradation in lysosomes and is recycled. The cellular location and mechanism by which FcRn protects albumin are partially understood...
March 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28329820/hepatocellular-toxicity-of-imidazole-and-triazole-antimycotic-agents
#10
Patrizia Haegler, Lorenz Joerin, Stephan Krähenbühl, Jamal Bouitbir
Hepatotoxicity has been described for all antimycotic azoles currently marketed. A possible mechanism involving mitochondrial dysfunction has been postulated for ketoconazole, but not for the other azoles. The aim of the current investigations was to study the toxicity of different azoles in human cell models and to find out mechanisms of their toxicity. In HepG2 cells, posaconazole and ketoconazole were cytotoxic starting at 20 and 50 µM and decreased the cellular ATP content starting at 5 and 10 µM, respectively...
January 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28328144/diagnosing-and-preventing-iron-overload
#11
Ganesh Ramanathan, John K Olynyk, Paolo Ferrari
Absolute or functional iron (Fe) deficiency is an important determinant of anemia in hemodialysis patients and parenteral Fe is routinely used to treat this condition in conjunction with erythropoiesis stimulating agents. While restoration of hemoglobin toward the target range is a good outcome of Fe replacement, it is well known that Fe overload and toxicity may be adverse consequences of this therapy. Dialysis clinical practice guidelines recommend tailoring Fe therapy based on transferrin saturation and serum ferritin levels...
March 22, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28327127/effects-of-vitellaria-paradoxa-c-f-gaertn-aqueous-leaf-extract-administration-on-salmonella-typhimurium-infected-rats
#12
Siméon Pierre Chegaing Fodouop, Sedric Donald Tala, Lunga Paul Keilah, Norbert Kodjio, Mefokou Didiane Yemele, Armel Herve Kamdje Nwabo, Bridget Nji-Kah, Joseph Tchoumboue, Donatien Gatsing
BACKGROUND: The present study investigates the effects of Vitellaria paradoxa crude extract administration on Salmonella typhimurium infected Wistar rats. METHODS: Rats were infected by single dose oral administration of Salmonella typhimurium (1.5×10(8) CFU). Negative control groups were infected and treated orally with distilled water (vehicle), neutral control group were not infected, while the four test groups were treated up to 18 days with 55 mg/kg, 110 mg/kg, 220 mg/kg and 440 mg/kg body weight of aqueous extract of V...
March 21, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28324255/can-red-deer-antlers-be-used-as-an-indicator-of-environmental-and-edible-tissues-trace-element-contamination
#13
Aleksandra Giżejewska, Józef Szkoda, Agnieszka Nawrocka, Jan Żmudzki, Zygmunt Giżejewski
Venison is an attractive product for consumers concerned with healthy lifestyle; however, it can contain high levels of toxic elements, and therefore, it is a possible source of hazardous contaminants in human diet. Antlers are suitable bioindicators of environmental metal contamination, and herein, we assessed the ability of trace element levels in antlers to indicate levels in edible soft tissues. We determined the concentrations of lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), copper (Cu), zinc (Zn), and iron (Fe) in the liver, kidney, muscle, and antlers of 14 free-ranging red deer (Cervus elaphus) from northeastern Poland using atomic absorption spectrometry...
March 21, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28323213/oral-delivery-of-bacillus-subtilis-spores-expressing-cysteine-protease-of-clonorchis-sinensis-to-grass-carp-ctenopharyngodon-idellus-induces-immune-responses-and-has-no-damage-on-liver-and-intestine-function
#14
Zeli Tang, Hengchang Sun, TingJin Chen, Zhipeng Lin, Hongye Jiang, Xinyi Zhou, Cunbin Shi, Houjun Pan, Ouqin Chang, Pengli Ren, Jinyun Yu, Xuerong Li, Jin Xu, Yan Huang, Xinbing Yu
Clonorchis sinensis (C. sinensis) is a fish-borne trematode. Human can be infected by ingestion of C. sinensis metacercariae parasitized in grass carp (Ctenopharyngodon idella). For induction of effective oral immune responses, spores of Bacillus subtilis (B. subtilis) WB600 were utilized as vehicle to delivery CsCP (cysteine protease of C. sinensis) cooperated with CotC (B.s-CotC-CP), one of coat proteins, to the gastrointestinal tract. After routine culture of 8-12 h in LB medium, B. subtilis containing CotC-CsCP was transferred into the sporulation culture medium...
March 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28323199/acute-toxicity-bioaccumulation-and-effects-of-dietary-transfer-of-silver-from-brine-shrimps-exposed-to-pvp-pei-coated-silver-nanoparticles-to-zebrafish
#15
José María Lacave, Álvaro Fanjul, Eider Bilbao, Nerea Gutierrez, Irantzu Barrio, Inmaculada Arostegui, Miren P Cajaraville, Amaia Orbea
The extensive use and release to the aquatic environment of silver nanoparticles (NPs) could lead to their incorporation into the food web. Brine shrimp larvae of 24h showed low sensitivity to the exposure to PVP/PEI-coated Ag NPs (5nm), with EC50 values at 24h of 19.63mg Ag L(-1), but they significantly accumulated silver after 24h of exposure to 100μg L(-1) of Ag NPs. Thus, to assess bioaccumulation and effects of silver transferred by the diet in zebrafish, brine shrimp larvae were exposed to 100ng L(-1) of Ag NPs as an environmentally relevant concentration or to 100μg L(-1) as a potentially effective concentration and used to feed zebrafish for 21days...
March 16, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28323103/cr-vi-induces-cytotoxicity-in-vitro-through-activation-of-ros-mediated-endoplasmic-reticulum-stress-and-mitochondrial-dysfunction-via-the-pi3k-akt-signaling-pathway
#16
Yujing Zhang, Fang Xiao, Xinmin Liu, Kaihua Liu, Xiaoxin Zhou, Caigao Zhong
The occupational and environmental toxicant hexavalent chromium [Cr(VI)] can cause severe damage to the liver; however, the exact mechanisms associated with its toxicity have not been thoroughly demonstrated. In the present study, the underlying mechanisms of Cr(VI)-induced hepatotoxicity were investigated. Our results showed that Cr(VI) inhibited the growth and proliferation of L-02 hepatocytes. Further study revealed that Cr(VI) significantly induced S-phase cell cycle arrest and apoptosis accompanying with the overproduction of reactive oxygen species (ROS)...
March 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28322867/bile-acid-analysis-in-human-disorders-of-bile-acid-biosynthesis
#17
REVIEW
Frédéric M Vaz, Sacha Ferdinandusse
Bile acids facilitate the absorption of lipids in the gut, but are also needed to maintain cholesterol homeostasis, induce bile flow, excrete toxic substances and regulate energy metabolism by acting as signaling molecules. Bile acid biosynthesis is a complex process distributed across many cellular organelles and requires at least 17 enzymes in addition to different metabolite transport proteins to synthesize the two primary bile acids, cholic acid and chenodeoxycholic acid. Disorders of bile acid synthesis can present from the neonatal period to adulthood and have very diverse clinical symptoms ranging from cholestatic liver disease to neuropsychiatric symptoms and spastic paraplegias...
March 17, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28322830/antidiabetic-antidyslipidemic-and-toxicity-profile-of-env-2-a-potent-pyrazole-derivative-against-diabetes-and-related-diseases
#18
Eduardo Hernández-Vázquez, Hugo Ocampo-Montalban, Litzia Cerón-Romero, Miguel Cruz, Jaime Gomez-Zamudio, Guadalupe Hiriart-Valencia, Rafael Villalobos-Molina, Angelica Flores-Flores, Samuel Estrada-Soto
Diabetes is a major health problem and a predisposition factor for further degenerative complications and, therefore, novel therapies are urgently needed. Currently, cannabinoid receptor 1 (CB1 receptor) antagonists have been considered as promissory entities for metabolic disorders treatment. Accordingly, the purpose of this work was the evaluation of the sub-acute antidiabetic, anti-hyperglycemic, antidyslipidemic and toxicological profile of ENV-2, a potent hypoglycemic and antioxidant CB1 receptor antagonist...
March 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28322544/graphene-oxide-quantum-dots-as-novel-nanozymes-for-alcohol-intoxication
#19
Anqi Sun, Li Mu, Xiangang Hu
Alcohol overconsumption as a worldwide issue results in alcoholic liver disease (ALD), such as steatosis, alcoholic hepatitis and cirrhosis. The treatment of ALD has been widely investigated but remains challenging. In this work, the protective effects of graphene oxide quantum dots (GOQDs) as novel nanozymes against alcohol overconsumption are discovered, and the specific mechanisms underlying these effects are elucidated via omics analysis. GOQDs dramatically alleviate the reduction of cell viability induced by ethanol and can act as nanozymes to accelerate ethanol metabolism and avoid the accumulation of toxic intermediates in cells...
March 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28321998/moderate-selenium-dosing-inhibited-chromium-vi-toxicity-in-chicken-liver
#20
Yang Wang, Yongxia Liu, Huiyu Wan, Yiran Zhu, Peng Chen, Pan Hao, Ziqiang Cheng, Jianzhu Liu
This study aimed to clarify the effect of selenium (Se) on chromium (VI) [Cr(VI)]-induced damage in chicken liver. A total of 105 chickens were randomly divided into seven groups of 15. Group I received deionized water; group II received Cr(VI) (7.83 mg/kg/d) alone; and other groups orally received both Cr(VI) (7.83 mg/kg/d) and Se of different doses (0.14, 0.29, 0.57, 1.14, and 2.28 mg/kg/d). The levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), Ca(2+) -ATPase, and mitochondrial membrane potential (MMP) were measured...
March 21, 2017: Journal of Biochemical and Molecular Toxicology
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