Search results for "Chemical and Drug Induced Liver Injury"
showing 10 items of 66 documents
Nephrotoxic and hepatotoxic effects of chromium compounds in rats
1986
The nephrotoxic, hepatotoxic and cardiotoxic actions of hexavalent chromium compounds, as well as their effects on lung, blood and circulation may contribute to the fatal outcome of chromium intoxication. Although trivalent chromium have been regarded as relatively biologically inert, there are a few salts of chromium III that have been found to be carcinogenic when inhaled, ingested or brought in contact with the tissues. Sensitive persons and industry workers have been subjects of dermatitis, respiratory tract injuries and digestive ulcers due to chromium compounds. In this work, the authors have studied the effect of trivalent and hexavalent chromium compounds on rats measuring the trans…
Compromising mitochondrial function with the antiretroviral drug efavirenz induces cell survival-promoting autophagy
2011
Hepatotoxicity is a very common side effect associated with the pharmacological treatment of human immunodeficiency virus (HIV) infection and its pathogenesis is poorly understood. Efavirenz (EFV) is the most widely used nonnucleoside reverse transcriptase inhibitor administered for the control of HIV and some of its toxic effects in hepatic cells have been recently shown to display features of mitochondrial dysfunction. Here we studied the activation of autophagy and, in particular, mitophagy, the main mitochondrial turnover mechanism, in human hepatic cells treated with clinically relevant concentrations of this drug. EFV-treated cells had altered mitochondria, characterized by a relative…
Mechanism-based selection of compounds for the development of innovative in vitro approaches to hepatotoxicity studies in the LIINTOP project.
2010
The 6th European Framework Programme project LIINTOP was specifically raised to optimise and provide established protocols and experimental in vitro models for testing intestinal and liver absorption, metabolism and toxicity of molecules of pharmacological interest. It has been focused on some of the most promising existing liver and intestine in vitro models with the aim of further improving their performance and thus taking them to a pre-normative research stage. Regarding the specific area of the liver, a first basic approach was the optimisation of in vitro hepatic models and the development and optimisation of in vitro approaches for toxicity screening. New advanced technologies have b…
Adverse drug reaction and organ damage: the liver
2016
Drug-induced liver injury (DILI) is among the most challenging acute or chronic liver conditions to be handled by physicians. Despite its low incidence in the general population, DILI is a frequent cause of acute liver failure. As such, the possibility of DILI should be considered in all patients who present with acute liver damage, independent of any known pre-existing liver disease. DILI can be classified as intrinsic/dose-dependent (e.g., acetaminophen toxicity) or idiosyncratic/dose-independent, with the latter form being relatively uncommon. Amoxicillin-clavulanate is the antimicrobial that is most frequently associated with idiosyncratic DILI. Large, ongoing, prospective studies in we…
Development of a Multiparametric Cell-based Protocol to Screen and Classify the Hepatotoxicity Potential of Drugs
2012
Hepatotoxicity is a major reason for drug nonapprovals and withdrawals. The multiparametric analysis of xenobiotic toxicity at the single cells level using flow cytometry and cellular imaging-based approaches, such as high-content screening (HCS) technology, could play a key role in the detection of toxicity and the classification of compounds based on patterns of cellular injury. This study aimed to develop and validate a practical, reproducible, in vitro multiparametric cell-based protocol to assess those drugs that are potentially hepatotoxic to humans and to suggest their mechanisms of action. The assay was applied to HepG2 human cell line cultured in 96-well plates and exposed to 78 di…
Herbal hepatotoxicity: a hidden epidemic
2011
Complementary and alternative therapies, including herbal products, have become increasingly popular in the general population and among patients and physicians. Regulations and pharmacovigilance regarding herbal drugs are still incomplete and need to be improved. In fact, herbals are commonly marketed on the Internet, and in many countries they are sold as food supplements, which are beyond the control of drug regulatory agencies. In Europe and the U.S., reports of hepatotoxicity from these products, including those advertised for liver diseases, are accumulating. Many herbal drugs are also commonly used in children, and in women during pregnancy and lactation, because they are believed to…
Novel Biocompatible Cationic Copolymers Based on Polyaspartylhydrazide Being Potent as Gene Vector on Tumor Cells
2007
Introduction. The reaction between !,"-poly(aspartylhydrazide) (PAHy), a water soluble synthetic polymer and 3-(carboxypropyl)trimethyl-ammonium chloride (CPTACl) produced copolymers bearing permanent positive charges (PAHy–CPTA) with molecular weight of 10 kDa and PAHy–CPTA copolymers differing in positive charge amount (18–58%) were chosen for biological investigations. Materials and methods. Biophysical properties of DNA/PAHy–CPTA polyplexes were evaluated in terms of DNA condensation, zeta potential and size distribution. Cytotoxicity studies on Neuro2A murine neuroblastoma cells evidenced absence of toxicity of these copolymers up to 300 2g/ml unlike linear polyethylenimine (LPEI) that…
In vivo confocal laser laparoscopy allows real time subsurface microscopy in animal models of liver disease.
2007
Background/Aims Histopathology is essential in the diagnostic workup of most liver diseases. However, biopsy sampling might carry risks, is subject to sampling error, and does not provide dynamic tissue imaging. Therefore a newly developed miniaturised confocal probe was evaluated for in vivo microscopic imaging in rodent models of human liver diseases. Methods The handheld laparoscopy probe used a 488nm single line laser for fluorophore excitation. Optical slice thickness was 7μm, lateral resolution 0.7μm. Imaging depth was 0–250μm below the tissue surface. Imaging using different fluorescent staining protocols was performed in healthy mice, IFNγ- and IL-12-induced hepatitis, after bile du…
Ablation of c-FLIP in hepatocytes enhances death-receptor mediated apoptosis and toxic liver injury in vivo
2010
Background & Aims Apoptosis is crucially involved in acute and chronic liver injury, including viral, cholestatic, toxic, and metabolic liver disease. Additionally, dysregulation of apoptosis signaling pathways has been implicated in hepatocarcinogenesis. The most prominent members of the apoptosis-mediating tumor necrosis factor receptor superfamily are the TNF-R1 (CD120a) and the CD95 (Apo-1/Fas) receptor. Although extensively studied, the intracellular signaling events in hepatocytes are only incompletely understood. Methods To examine the role of the caspase-8 homolog cellular FLICE-inhibitory protein (c-FLIP) in liver injury, we generated mice with hepatocyte specific deletion of c-FLI…
Increased hepatic fibrosis and JNK2-dependent liver injury in mice exhibiting hepatocyte-specific deletion of cFLIP.
2012
Chronic liver disease promotes hepatocellular injury involving apoptosis and triggers compensatory regeneration that leads to the activation of quiescent stellate cells in the liver. The deposition of extracellular matrix from activated myofibroblasts promotes hepatic fibrosis and the progression to cirrhosis with deleterious effects on liver physiology. The role of apoptosis signaling pathways in the development of fibrosis remains undefined. The aim of the current study was to determine the involvement of the caspase-8 homologue cellular FLICE-inhibitory protein (cFLIP) during the initiation and progression of fibrosis. Liver injury and fibrosis from carbon tetrachloride (CCl4) and thioa…