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https://www.readbyqxmd.com/read/29161501/phenanthrene-induced-apoptosis-and-its-underlying-mechanism
#1
Xiangsheng Hong, Jianhui Qin, Rui Chen, Lilai Yuan, Jinmiao Zha, Chao Huang, Na Li, Xiaoya Ji, Zijian Wang
Phenanthrene (Phe) is one of the most abundant low-molecular-weight polycyclic aromatic hydrocarbons (PAHs). Widespread human and aquatic organism exposure to Phe has been reported, but the toxic effects of Phe and potential mechanisms are unclear. We focused on the chronic hepatotoxicity of Phe in adult Chinese rare minnows (Gobiocypris rarus) and the underlying mechanisms. The chronic effects of exposing Chinese rare minnows to 8.9, 82.3, or 510.0 μg/L Phe for 30 days were examined by histopathological observation, TUNEL assays, caspase activity assays, and gene expression profiles...
November 21, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29159701/residues-of-diclofenac-in-tissues-of-vultures-in-india-a-post-ban-scenario
#2
Kanthan Nambirajan, Subramanian Muralidharan, Aditya A Roy, S Manonmani
Populations of three resident Gyps species (Indian white-backed vulture Gyps bengalensis, Indian vulture Gyps indicus, and Slender-billed vulture Gyps tenuirostris) in India have decreased by more than 90% since mid 1990s, and they continue to decline. Experimental studies showed the mortality of vultures to be due to renal failure caused by diclofenac, a nonsteroidal anti-inflammatory drug. India, Pakistan, and Nepal banned the veterinary usage of diclofenac in 2006 to prevent further decline in vulture population...
November 20, 2017: Archives of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/29159461/severe-hyperammonemic-encephalopathy-requiring-dialysis-aggravated-by-prolonged-fasting-and-intermittent-high-fat-load-in-a-ramadan-fasting-month-in-a-patient-with-cptii-homozygous-mutation
#3
P Phowthongkum, C Ittiwut, V Shotelersuk
BACKGROUND: Carnitine palmitoyltransferase II (CPTII) deficiency is a mitochondrial fatty acid oxidation disorder that can present antenatally as congenital brain malformations, or postnatally with lethal neonatal, severe infantile, or the most common adult myopathic forms. No case of severe hyperammonemia without liver dysfunction has been reported. CASE PRESENTATION: We described a 23-year-old man who presented to the emergency department with seizures and was found to have markedly elevation of serum ammonia...
November 21, 2017: JIMD Reports
https://www.readbyqxmd.com/read/29158815/tethering-interleukin-22-to-apolipoprotein-a-i-ameliorates-mice-from-acetaminophen-induced-liver-injury
#4
Wei Chen, Xuyao Zhang, Jiajun Fan, Wenjing Zai, Jingyun Luan, Yubin Li, Shaofei Wang, Qicheng Chen, Yichen Wang, Yanxu Liang, Dianwen Ju
Increasing evidence indicates that interleukin-22 (IL-22) holds tremendous potential as a protective agent in preventing liver injury, but its pleiotropic effects and pathogenic role in carcinogenesis, rheumatoid arthritis and psoriasis restrict its systemic application. Here, we first developed a nanoparticle (liposIA) as a liver-targeted agent through IL-22 tethered to apolipoprotein A-I (ApoA-I) in a gene therapy vector. LiposIA was prepared using thin film dispersion method and the complexes exhibited desirable nanoparticle size, fine polydisperse index, highly efficient transfection, and excellent serum and storage stability...
2017: Theranostics
https://www.readbyqxmd.com/read/29158365/phase-ii-trial-using-a-combination-of-oxaliplatin-capecitabine-and-celecoxib-with-concurrent-radiation-for-newly-diagnosed-resectable-rectal-cancer
#5
Emilio P Araujo-Mino, Yehuda Z Patt, Cristina Murray-Krezan, Joshua A Hanson, Pranshu Bansal, Ben J Liem, Ashwani Rajput, M Houman Fekrazad, Glenory Heywood, Fa Chyi Lee
LESSONS LEARNED: Colorectal cancers exhibit a high level of cyclooxygenase-2 (COX-2) expression with strong preclinical rationale for improved clinical outcomes with COX-2 inhibition. Celecoxib is a COX-2 inhibitor and we have shown that it can be safely combined with capecitabine and oxaliplatin as part of neoadjuvant treatment with radiation therapy (RT) in rectal cancer.There was a significant improvement in skin toxicity with this combination as compared with historical data. Considering the field has moved on to single-agent capecitabine, we believe future trials with capecitabine and celecoxib hold potential...
November 20, 2017: Oncologist
https://www.readbyqxmd.com/read/29157977/cell-type-specific-pharmacological-kinase-inhibition-for-cancer-chemoprevention
#6
Manjeet Deshmukh, Shigeki Nakagawa, Takaaki Higashi, Adam Vincek, Anu Venkatesh, Marina Ruiz de Galarreta, Anna P Koh, Nicolas Goossens, Hadassa Hirschfield, C Billie Bian, Naoto Fujiwara, Atsushi Ono, Hiroki Hoshida, Mohamed El-Abtah, Noor B Ahmad, Amaia Lujambio, Roberto Sanchez, Bryan C Fuchs, Klaas Poelstra, Jai Prakash, Yujin Hoshida
Safety is prerequisite for preventive medicine, but non-toxic agents are generally ineffective as clinical chemoprevention. Here we propose a strategy overcoming this challenge by delivering molecular-targeted agent specifically to the effector cell type to achieve sufficient potency, while circumventing toxicity in the context of cancer chemoprevention. Hepatic myofibroblasts drive progressive fibrosis that results in cirrhosis and liver cancer. In a rat model of cirrhosis-driven liver cancer, a small molecule epidermal growth factor receptor inhibitor, erlotinib, was delivered specifically to myofibroblasts by a versatile nanoparticle-based system, targeting platelet-derived growth factor receptor-beta uniquely expressed on their surface in the liver...
November 17, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29157287/safety-in-treatment-of-hepatocellular-carcinoma-with-immune-checkpoint-inhibitors-as-compared-to-melanoma-and-non-small-cell-lung-cancer
#7
Zachary J Brown, Bernd Heinrich, Seth M Steinberg, Su Jong Yu, Tim F Greten
BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem worldwide with increasing incidence rates. As HCC traditionally occurs in chronically inflamed livers, this inflammation aids to drive oncogenesis and often renders these lesions to be immunogenic and therefore potential targets for immunotherapy. As patients with HCC generally have underlying liver dysfunction, we sought to determine if immune checkpoint inhibitors were safe to use in patients with HCC as compared to melanoma and non-small cell lung cancer (NSCLC) in terms of the gastrointestinal side effects of elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and diarrhea as well as patients who drop out of the study due to drug toxicity and death secondary to drug toxicity...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29156995/combined-repeated-dose-and-reproductive-developmental-toxicity-screening-test-of-benzene-1-1-oxybis-tetrapropylene-derivs-in-rats
#8
Yasuhiro Tsubokura, Ryuichi Hasegawa, Sunao Aso, Toshio Kobayashi, Takayuki Koga, Satsuki Hoshuyama, Yutaka Oshima, Katsumi Miyata, Yuji Kusune, Takako Muroi, Naoki Hashizume, Yoshiyuki Inoue, Shozo Ajimi, Kotaro Furukawa
We have conducted animal toxicity tests of chemicals for a chemical safety program implemented by the Ministry of Economy, Trade and Industry of Japan. Here we conducted a combined repeated-dose and reproductive/developmental toxicity screening test of benzene, 1,1'-oxybis-, tetrapropylene derivs. (BOTD). BOTD was administered to 9-week-old Crl:CD(SD) male and female rats by gavage at 0, 40, 200, or 1000 mg/kg/day. Males were treated for 42 days including mating period. Females were treated for 42-53 days through the premating, mating, pregnancy, and until Day 4 of lactation periods...
November 20, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29156755/escherichia-coli-nissle-1917-engineered-to-express-tum-5-can-restrain-murine-melanoma-growth
#9
Lian He, Huijun Yang, Fei Liu, Yiyan Chen, Sijia Tang, Wei Ji, Jianli Tang, Zhudong Liu, Yunjun Sun, Shengbiao Hu, Youming Zhang, Xiong Liu, Weitao Huang, Xuezhi Ding, Liqiu Xia
Tumor growth and metastasis depend on angiogenesis. Thus, inhibiting tumor angiogenesis has become promising cancer therapeutic strategy in recent years. Tumstatin is a more powerful angiogenesis inhibitor than endostatin. Anti-angiogenic active fragment encoding amino acids 45-132 (Tum-5) of tumstatin was subcloned into four different inducible expression vectors and successfully solubly expressed in Escherichia coli BL21 (DE3) in this study. Subsequently, an anaerobic inducible expression vector was constructed under Vitreoscilla hemoglobin gene promoter Pvhb in E...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156531/heated-naringin-mitigate-the-genotoxicity-effect-of-mitomycin-c-in-balb-c-mice-through-enhancing-the-antioxidant-status
#10
Mouna Maatouk, Nadia Mustapha, Imen Mokdad-Bzeouich, Hind Chaaban, Irina Ioannou, Kamel Ghedira, Mohamed Ghoul, Leila Chekir-Ghedira
A major problem with cancer chemotherapy is its severe toxic effects on non-target tissues. Assessment of natural products for their protective effect against anticancer drugs induced toxicity is gaining importance in cancer biology. The aim of the present study was to evaluate the effect of native and thermal treated naringin on the protective effect against mitomycin C (MMC) induced genotoxicity. The genotoxicity in liver kidney and brain cells isolated from Balb/C mice were evaluated by performing the comet assay...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156491/long-term-calcineurin-inhibitor-therapy-and-brain-function-in-patients-after-liver-transplantation
#11
Henning Pflugrad, Anna-Kristina Schrader, Anita Blanka Tryc, Xiaoqi Ding, Heinrich Lanfermann, Elmar Jäckel, Harald Schrem, Jan Beneke, Hannelore Barg-Hock, Jürgen Klempnauer, Karin Weissenborn
BACKGROUND AND AIMS: Calcineurin inhibitors (CNI) frequently induce neurological complications early after orthotopic liver transplantation (OLT). We hypothesize that long-term CNI therapy after OLT causes dose-dependent cognitive dysfunction and alteration of brain structure. METHODS: Eighty-five OLT patients (20 with CNI free, 35 with CNI low dose and 30 with standard dose CNI immunosuppression) underwent psychometric testing and cerebral magnetic resonance tomography about 10 years after OLT to assess brain function and structural brain alterations...
November 20, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/29156373/mitochondria-targeted-ubiquinone-mitoq-enhances-acetaldehyde-clearance-by-reversing-alcohol-induced-posttranslational-modification-of-aldehyde-dehydrogenase-2-a-molecular-mechanism-of-protection-against-alcoholic-liver-disease
#12
Liuyi Hao, Qian Sun, Wei Zhong, Wenliang Zhang, Xinguo Sun, Zhanxiang Zhou
Alcohol metabolism in the liver generates highly toxic acetaldehyde. Breakdown of acetaldehyde by aldehyde dehydrogenase 2 (ALDH2) in the mitochondria consumes NAD(+) and generates reactive oxygen/nitrogen species, which represents a fundamental mechanism in the pathogenesis of alcoholic liver disease (ALD). A mitochondria-targeted lipophilic ubiquinone (MitoQ) has been shown to confer greater protection against oxidative damage in the mitochondria compared to untargeted antioxidants. The present study aimed to investigate if MitoQ could preserve mitochondrial ALDH2 activity and speed up acetaldehyde clearance, thereby protects against ALD...
November 11, 2017: Redox Biology
https://www.readbyqxmd.com/read/29156308/modulatory-effects-of-green-tea-extract-against-the-hepatotoxic-effects-of-4-nonylphenol-in-catfish-clarias-gariepinus
#13
A H Sayed, Hamdy A M Soliman
The antioxidant role of the green tea (Camellia sinensis) extract (GTE) was examined to remedy the toxic effects of (0.2mgl(-1)) 4-nonylphenol(4-NP). Biochemical parameters, antioxidant enzymes, liver lipid peroxidation (LPO), DNA fragmentation, and apoptosis as well as histopathology of liver of African catfish Clarias gariepinus were considered. Catfishes were divided into four groups: first group (control), second group (0.2mgl(-1) of 4-NP), third group (0.2mgl(-1)of 4-NP +100mg GTE l(-1)water), and fourth group (0...
November 17, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29155963/generating-modelling-data-from-repeat-dose-toxicity-reports
#14
Oriol López-Massaguer, Kevin Pinto-Gil, Ferran Sanz, Alexander Amberg, Lennart T Anger, Manuela Stolte, Carlo Ravagli, Philippe Marc, Manuel Pastor
Over the past decades, pharmaceutical companies have conducted a large number of high quality in vivo repeat-dose toxicity (RDT) studies for regulatory purposes. As part of the eTOX project, a high number of these studies have been compiled and integrated into a database. This valuable resource can be queried directly, but it can be further exploited to build predictive models. As the studies were originally conducted to investigate the properties of individual compounds, the experimental conditions across the studies are highly heterogeneous...
November 16, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29155486/toxic-stress-and-child-refugees
#15
John S Murray
The purpose of this article was to describe the phenomenon of toxic stress and its impact on the physical and mental health of child refugees. Almost two decades ago, researchers found that recurring adverse childhood events (ACEs; e.g., physical, psychological, and sexual abuse, neglect, and household dysfunction such as substance abuse, mental illness, and criminal behavior) were associated with a significant increase in serious illnesses during adulthood. Illnesses include heart, lung, and liver disease, cancer, and bone fractures...
November 20, 2017: Journal for Specialists in Pediatric Nursing: JSPN
https://www.readbyqxmd.com/read/29154964/lipotoxicity-and-the-gut-liver-axis-in-nash-pathogenesis
#16
REVIEW
Fabio Marra, Gianluca Svegliati-Baroni
The pathogenesis of nanoalcoholic fatty liver disease is still incompletely understood, in particolar the mechanisms whereby a minority of patients develop a more severe phenotype characterized by hepatocellular damage, inflammation, and fibrosis. In this review we discuss two pivotal aspects of the pathogenesis of NASH. We first analyze the initial mechanisms responsible of hepatocellular damage and inflammation, which derive from the toxic effects of excess lipids. Accumulating data indicate that the total amount of triglycerides stored in hepatocytes is not the major determinant of lipotoxicity, and that specific lipid classes act as damaging agents on liver cells...
November 14, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29154799/integrative-omics-data-analyses-of-repeated-dose-toxicity-of-valproic-acid-in-vitro-reveal-new-mechanisms-of-steatosis-induction
#17
Simone G J van Breda, Sandra M H Claessen, Marcel van Herwijnen, Daniël H J Theunissen, Danyel G J Jennen, Theo M C M de Kok, Jos C S Kleinjans
Valproic acid (VPA) is a very potent anti-cancer and neuro-protective drug probably by its HDAC inhibiting properties, which may cause steatosis in the liver. The present study investigates the effect of repetitive VPA treatment of primary human hepatocytes (PHH) on whole genome gene expression-, DNA methylation-, and miRNA changes, using microarrays and integrated data analyses. PHH were exposed to a non-cytotoxic dose of VPA for 5days daily which induced lipid accumulation. Part of the PHH was left untreated for 3days for studying the persistence of 'omics' changes...
November 14, 2017: Toxicology
https://www.readbyqxmd.com/read/29154121/trace-elements-in-the-liver-of-captive-and-free-ranging-european-bison-bison-bonasus-l
#18
Maciej Durkalec, Agnieszka Nawrocka, Michał Krzysiak, Magdalena Larska, Mirosława Kmiecik, Andrzej Posyniak
European bison is classified as a vulnerable species because of many threats. We analyzed the content of toxic and essential elements (Ag, Al, As, Ba, Be, Cd, Co, Cr, Cu, Hg, Mg, Mn, Na, Ni, Pb, Se, Th, Tl, U, V, and Zn) in the livers of 30 captive and free-ranging European bison from the Bison Breeding Center in Smardzewice and from Białowieża Primeval Forest in Poland. The contents of toxic elements were lower than reported previously in European Bison and were similar to those of wild ungulates from non-polluted areas...
November 13, 2017: Chemosphere
https://www.readbyqxmd.com/read/29153377/iatrogenic-iron-overload-and-its-potential-consequences-in-patients-on-hemodialysis
#19
Guy Rostoker, Nosratola D Vaziri
Iron overload was considered rare in hemodialysis patients until recently, but its clinical frequency is now increasingly recognized. The liver is the main site of iron storage and the liver iron concentration (LIC) is closely correlated with total iron stores in patients with secondary hemosiderosis and genetic hemochromatosis. Magnetic resonance imaging (MRI) is now the gold standard method for estimating and monitoring LIC. Studies of LIC in hemodialysis patients by magnetic susceptometry thirteen years ago and recently by quantitative MRI have demonstrated a relation between the risk of iron overload and the use of intravenous (IV) iron products prescribed at doses determined by the iron biomarker cutoffs contained in current anemia management guidelines...
November 16, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/29152699/comparative-analysis-of-the-protective-effects-of-curcumin-and-n-acetyl-cysteine-against-paracetamol-induced-hepatic-renal-and-testicular-toxicity-in-wistar-rats
#20
Zeynab Kh El-Maddawy, Yasser S El-Sayed
This study aimed to investigate the possible protective role of curcumin (CUR) vs. N-acetyl cysteine (NAC) against paracetamol (PCM)-induced oxidative damage and impairment of liver, kidney, and testicular functions, as well as hematotoxicity, in albino rats. A large single dose of PCM induced lipid peroxidation along with a significant decline in glutathione content and catalase activity in the liver, kidneys, and testicles. The apparent oxidative damage was associated with evident hepatic, renal, and testicular dysfunction, which was confirmed in histopathological lesions, and increased serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activities...
November 19, 2017: Environmental Science and Pollution Research International
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