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liver toxicity

Serli Önlü, Melek Türker Saçan
The authors constructed novel, robust and validated linear Quantitative Structure-Toxicity Relationship (QSTR) models in line with OECD criteria using the two cytotoxicity data sets which were obtained from the Alamar Blue (AB) and 5-carboxyfluorescein diacetate acetoxymethyl ester (CFDA-AM) assays. The data sets comprise the cytotoxic effect of structurally diverse and widely used pharmaceuticals, synthetic musks and industrial chemicals on the rainbow trout (Oncorhynchus mykiss) liver cell line RTL-W1. Common descriptors defined the relationship between structure and cytotoxicity for both the AB and the CFDA-AM assays which measure the metabolic activity and membrane integrity, respectively...
October 25, 2016: Environmental Toxicology and Chemistry
S A Harrison, S R Marri, N Chalasani, R Kohli, W Aronstein, G A Thompson, W Irish, M V Miles, S A Xanthakos, E Lawitz, M Noureddin, T D Schiano, M Siddiqui, A Sanyal, B A Neuschwander-Tetri, P G Traber
BACKGROUND: Non-alcoholic steatohepatitis (NASH) and resultant liver fibrosis is a major health problem without approved pharmacotherapy. Pre-clinical results of GR-MD-02, a galectin-3 inhibitor, suggested potential efficacy in NASH with advanced fibrosis/cirrhosis and prompted initiation of a clinical development programme in NASH with advanced fibrosis. AIM: To evaluate the safety, pharmacokinetics and exploratory pharmacodynamic markers of GR-MD-02 in subjects having NASH with bridging fibrosis...
October 24, 2016: Alimentary Pharmacology & Therapeutics
Brian F Kiesel, Robert A Parise, Jianxia Guo, Donna M Huryn, Paul A Johnston, Raffaele Colombo, Malabika Sen, Jennifer R Grandis, Jan H Beumer, Julie L Eiseman
PURPOSE: The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) promotes gene transcription involved in cancer, and its activation by IL-6 is found in head and neck squamous cell carcinoma. Four triazolothiadizine STAT3 pathway inhibitors were evaluated to prioritize a single compound for in vivo examination. METHODS: Metabolic stability in mouse liver microsome incubation was used to evaluate four triazolothiadizine analogues, and UPCDC-10205 was administered to mice IV as single or multiple doses to evaluate toxicity...
October 24, 2016: Cancer Chemotherapy and Pharmacology
Anupam Ghosh, Anilava Kaviraj, Subrata Saha
Experiments with environmentally relevant concentrations of Cu in glass aquaria revealed that Cu was quickly removed from water. Cubic regression of Cu concentration against time showed that maximum rate of removal was around 69.34-72.11 h irrespective of treatment. The 96 h LC50 value of Cu was respectively 0.18, 0.19 and 0.35 mg/L for fish Cyprinus carpio, crustacean Diaptomus forbesi and worm Branchiura sowerbyi. Normalizing the lethal values and plotting them against time it was observed that there was sharp differences in mortality over time between the organisms and 96 h lethal values could misrepresent susceptibility of the organisms to Cu...
October 24, 2016: Bulletin of Environmental Contamination and Toxicology
Tahira Younis, Muhammad Rashid Khan, Moniba Sajid
BACKGROUND: Leaves and root bark of Fraxinus xanthoxyloides Wall. (Oleaceae) are used locally for the treatment of jaundice, malaria and pneumonia. Decoction of stem, twigs and bark is used in pain, internal injuries, rheumatism and in bone fracture. In this investigation we have evaluated the methanol extract of leaves for its hepatoprotective potential against CCl4 induced hepatic injuries in rat. METHODS: Powder of F. xanthoxyloides leaves was extracted with methanol (FXM) and subjected for the determination of polyphenolics through HPLC-DAD analysis...
October 24, 2016: BMC Complementary and Alternative Medicine
I Porreca, L Ulloa-Severino, P Almeida, D Cuomo, A Nardone, G Falco, M Mallardo, C Ambrosino
Several studies associate foetal human exposure to bisphenol A (BPA) to metabolic/endocrine diseases, mainly diabesity. They describe the role of BPA in the disruption of pancreatic beta cell, adipocyte and hepatocyte functions. Indeed, the complexity of the diabesity phenotype is due to the involvement of different endoderm-derived organs, all targets of BPA. Here, we analyse this point delineating a picture of different mechanisms of BPA toxicity in endoderm-derived organs leading to diabesity. Moving from epidemiological data, we summarize the in vivo experimental data of the BPA effects on endoderm-derived organs (thyroid, pancreas, liver, gut, prostate and lung) after prenatal exposure...
October 24, 2016: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Mohammad Islamuddin, Garima Chouhan, Muzamil Yaqub Want, Hani A Ozbak, Hassan A Hemeg, Farhat Afrin
BACKGROUND: The therapy of visceral leishmaniasis (VL) is limited by resistance, toxicity and decreased bioavailability of the existing drugs coupled with dramatic increase in HIV-co-infection, non-availability of vaccines and down regulation of cell-mediated immunity (CMI). Thus, we envisaged combating the problem with plant-derived antileishmanial drug that could concomitantly mitigate the immune suppression of the infected hosts. Several plant-derived compounds have been found to exert leishmanicidal activity via immunomodulation...
October 2016: PLoS Neglected Tropical Diseases
Harun-Or Rashid, Hyun-Kyoung Kim, Raghupatil Junjappa, Hyung-Ryong Kim, Han-Jung Chae
Compromised protein folding capacity in the endoplasmic reticulum (ER) leads to a protein traffic jam that produces a toxic environment called ER stress. However, the ER smartly handles such a critical situation by activating a cascade of proteins responsible for sensing and responding to the noxious stimuli of accumulated proteins. The ER protein load is higher in secretory cells, such as liver hepatocytes, which are thus prone to stress-mediated toxicity and various diseases, including alcohol-induced liver injury, fatty liver disease, and viral hepatitis...
October 23, 2016: Journal of Gastroenterology and Hepatology
Keren Bachi, Salvador Sierra, Nora D Volkow, Rita Z Goldstein, Nelly Alia-Klein
Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation in periphery and brain, decline in brain volume and function, and early onset of cardiac, cerebrovascular, kidney, and liver disease. Timely detection of accelerated aging in addiction is crucial for the prevention of premature morbidity and mortality...
February 2017: Current Opinion in Behavioral Sciences
Martin Uhl, Stefan Schwab, Thomas Efferth
A 52-year-old male patient was treated with standard radiochemotherapy with temozolomide for glioblastoma multiforme (GBM). After worsening of his clinical condition, further tumor-specific treatment was unlikely to be successful, and the patient seeked help from an alternative practitioner, who administered a combination of dichloroacetate (DCA) and artesunate (ART). A few days later, the patient showed clinical and laboratory signs of liver damage and bone marrow toxicity (leukopenia, thrombocytopenia). Despite successful restoration of laboratory parameters upon symptomatic treatment, the patient died 10 days after the infusion...
2016: Frontiers in Oncology
Hem Singh, Atish Prakash, A N Kalia, Abu Bakar Abdul Majeed
Previously explored combination therapies mostly involved the use of bioactive molecules. It is believed that herbal compounds containing multiple plant products have synergistic hepatoprotective effects and could enhance the desired actions. To investigate the combination of ethanolic fruits extract of Solanum xanthocarpum (SX) and Juniperus communis (JC) against Paracetamol (PCM) and Azithromycin (AZM) induced liver toxicity in rats. Liver toxicity was induced by combine oral administration of PCM (250 mg/kg) and AZM (200 mg/kg) for 7 days in Wistar rats...
October 2016: Journal of Traditional and Complementary Medicine
Walid Hamdy El-Tantawy
Lead is a toxic metal that induces a wide range of behavioral, biochemical and physiological effects in humans. Oxidative damage has been proposed as a possible mechanism involved in lead toxicity. The current study was carried out to evaluate the antioxidant activities of Spirulina supplement against lead acetate -induced hepatic injury in rats. Five groups of rats were used in this study, Control, Lead acetate (100 mg/kg), Lead acetate (100 mg/kg) + 0.5 g/kg Spirulina, Lead acetate (100 mg/kg) + 1 g/kg Spirulina and Lead acetate + 25 mg/100 g Vitamin C (reference drug)...
October 2016: Journal of Traditional and Complementary Medicine
Saganuwan Alhaji Saganuwan, Orinya Agbaji Orinya
Piroxicam is a benzothiazine compound with anti-inflammatory, antipyretic, and analgesic properties. Because of the very high efficacy of piroxicam and its increasing use in the treatment of carcinomas in dogs and cats, there is a need for acute toxicity study of piroxicam in monogastric animals and its potential for causing secondary poisoning in puppies. Piroxicam manufactured by Shanxi Federal Pharmaceutical Co, Ltd. was used for this study. Revised up-and-down procedure was used for the estimation of median lethal dose in mouse (259...
2016: Journal of Experimental Neuroscience
Chengwei Niu, Yuchen Sheng, Enyuan Zhu, Lili Ji, Zhengtao Wang
The rhizome of Dioscorea bulbifera Linn, traditionally used to treat thyroid disease and cancer in China, is reported to induce serious liver injury during clinical practice. Diosbulbin B (DB), a diterpene lactone, has been found to be the main toxic compound in D. bulbifera. The present study aims to investigate the protection of ferulic acid (FA) against DB-induced acute liver injury and its engaged mechanism. Mice were orally administered FA (20, 40, 80 mg/kg) once daily for 6 consecutive days; and then orally given DB (250 mg/kg) on the last day...
October 23, 2016: Bioscience Trends
Namrita Lall, Vivek Kumar, Debra Meyer, Nomasomi Gasa, Chris Hamilton, Motlalepula Matsabisa, Carel Oosthuizen
ETHNOPHARMACOLOGICAL RELEVANCE: The Natal gwarri or Natal ebony (Euclea natalensis A.DC.) is a deciduous tree found widespread throughout southern Africa, especially in Kwazulu-Natal and the southern cost. It has been widely used by indigenous communities such as the Zulus, Tsongas and Vendas for symptoms related to tuberculosis (TB). The decoctions made from the plant parts are administered for chest diseases to treat complications such as chest pains, bronchitis, pleurisy and asthma...
October 20, 2016: Journal of Ethnopharmacology
Rafaianne Queiroz Moraes-Souza, Thaigra Sousa Soares, Nágilla Orleanne Lima Carmo, Débora Cristina Damasceno, Kleber Eduardo Campos, Gustavo Tadeu Volpato
ETHNOPHARMACOLOGICAL RELEVANCE: Several women often use plant extracts during pregnancy without any concern about its possible toxic effects. The plant effects have been experimentally confirmed in animals and humans, while others require additional investigations. AIM OF STUDY: To evaluated the effect of aqueous extract of Croton urucurana latex on the maternal-fetal repercussions in rats. METHODS: Pregnant rats were randomly distributed into four experimental groups: Control=treated with water (vehicle); Treated 200=treated with a dose 200mg/kg; Treated 400= dose 400mg/kg and; and Treated 800= dose 800mg/kg...
October 20, 2016: Journal of Ethnopharmacology
Amit D Kadhare, Subhash L Bodhankar, V Mohan, Prasad A Thakurdesai
Vicenin-1 (fenugreek glycoside) has been proven to possess potent anti-inflammatory and anti-oxidant activity. The objective of the present investigation was to determine in-vivo acute and subacute (28-days repeated dose) oral toxicity of Vicenin-1 isolated from fenugreek seed. Vicenin-1 (93%) was isolated from a hydroalcoholic extract of fenugreek seed and characterized using HPLC, TLC, (1)H NMR and (13)C NMR. Acute oral toxicity (AOT) and subacute toxicity studies of Vicenin-1 were carried out according to OECD 425 (up-and-down procedure) and OCED 407 guidelines in Swiss albino mice...
October 20, 2016: Regulatory Toxicology and Pharmacology: RTP
Marcos Guilherme da Cunha, Gilson César Nobre Franco, Marcelo Franchin, John A Beutler, Severino Matias de Alencar, Masaharu Ikegaki, Pedro Luiz Rosalen
In silico and in vitro methodologies have been used as important tools in the drug discovery process, including from natural sources. The aim of this study was to predict pharmacokinetic and toxicity (ADME/Tox) properties of a coumarin isolated from geopropolis using in silico and in vitro approaches. Cinnamoyloxy-mammeisin (CNM) isolated from Brazilian M. scutellaris geopropolis was evaluated for its pharmacokinetic parameters by in silico models (ACD/Percepta™ and MetaDrug™ software). Genotoxicity was assessed by in vitro DNA damage signaling PCR array...
October 20, 2016: Toxicology Letters
Luqi Duan, John S Davis, Benjamin L Woolbright, Kuo Du, Mala Cahkraborty, James Weemhoff, Hartmut Jaeschke, Mohammed Bourdi
: Mouse models of acetaminophen (APAP) hepatotoxicity are considered relevant for the human pathophysiology. The C57BL/6 strain is most popular because it is the background strain of gene knock-out mice. However, conflicting results in the literature may have been caused by sub-strain mismatches, e.g. C57BL/6J and C57BL/6N. This study was initiated to determine the mechanism behind the sub-strain susceptibility to APAP toxicity. C57BL/6N and C57BL/6J mice were dosed with 200 mg/kg APAP and sacrificed at different time points...
October 20, 2016: Food and Chemical Toxicology
Kay Weng Choy, Nilika Wijeratne, James C G Doery
No abstract text is available yet for this article.
February 2016: Pathology
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