A large number of chemical agents, administered for therapeutic or diagnostic purposes, can produce various types of hepatic injury by several mechanisms. Some agents are intrinsically hepatotoxic, and others produce hepatic injury only in the rare, uniquely susceptible individual. Idiosyncrasy of the host is the mechanism for most types of drug-induced hepatic injury. It may reflect allergy to...

Male Wistar rats were treated with various model compounds or the appropriate vehicle controls in order to create a reference database for toxicogenomics assessment of novel compounds. Hepatotoxic compounds in the database were either known hepatotoxicants or showed hepatotoxicity during preclinical testing. Histopathology and clinical chemistry data were used to anchor the transcript profiles ...

Antibiotics used by general practitioners frequently appear in adverse-event reports of drug-induced hepatotoxicity. Most cases are idiosyncratic (the adverse reaction cannot be predicted from the drug's pharmacological profile or from pre-clinical toxicology tests) and occur via an immunological reaction or in response to the presence of hepatotoxic metabolites. With the exception of trovaflox...

I . It has been suggested that carbon tetrachloride damages rat liver by accelerating processes of lipid peroxidation at subcellular sites and that the protective action of vitamin E is due to its functioning as an antioxidant in vivo. Direct evidence for these mechanisms in vivo has been sought and is critically examined. 2. The increased production of malondialdehyde by rat liver microsomal f...

Carbon tetrachloride (CCl4), a hepatotoxic agent is widely used to study the toxic mechanisms in experimental animals. We have investigated whether oxidative stress is induced in the brain at a single hepatotoxic dosage (1 ml/kg bw) of CCl4. Increased lipid peroxidation (LPO), protein carbonyls (PC) content and glutathione (GSH) depletion were observed in the brain regions of rats treated with ...

The zebrafish embryo (ZFE) is a promising alternative, non-rodent model in toxicology, which has an advantage over the traditionally used models as it contains complete biological complexity and provides a medium to high-throughput setting. Here, we assess how the ZFE compares to the traditionally used models for liver toxicity testing, i.e., in vivo mouse and rat liver, in vitro mouse and rat ...

AIMS To report a new strategy for the detection of hepatotoxic adverse drug reactions (ADRs) in hospitalized patients improving the results obtained with other methods. DESIGN The model is based on the identification of a single alert signal in various target clinical departments over a 12-month period. Each patient was later interviewed following a set protocol. The main results analyzed wer...