Chemically defined serum-free media for rat hepatocytes have been useful in identifying EGFR ligands and HGF/MET signaling as direct mitogenic factors for rat hepatocytes. The absence of such media for mouse hepatocytes has prevented screening for discovery of such mitogens for mouse hepatocytes. We present results obtained by designing such a chemically defined medium for mouse hepatocytes and...

1,2-dichlorobenzene (1,2-DCB), an industrial solvent, is a known hepatotoxicant. Two oxidative events in the liver contribute to 1,2-DCB-induced liver injury: an initial hepatocellular oxidative stress, followed by oxidant stress associated with an inflammatory response. We hypothesize that the initial hepatocellular oxidative event triggers molecular and cellular processes within hepatocytes t...

The drug discovery and development process requires adequate safety testing for drug toxicity before new drugs can be administered to patients. Hepatocytes are used in vitro to screen compounds for hepatotoxicity, induction of drug-metabolizing enzymes such as cytochrome P450 (P450) isoforms, drug-drug interactions, and establish human relevance for metabolism. Cryopreservation makes it possibl...

Isolated rat and human hepatocytes in primary culture were shown to metabolize AAF to reactive intermediates which damaged hepatocyte DNA. A significant increase in unscheduled DNA synthesis was detectable by autoradiography in rat and human hepatocytes exposed to concentrations of AAF as low as 1 microM. When rat hepatocytes were plated over confluent monolayers of human fibroblasts and expose...

Cryopreserved hepatocytes are often used as a convenient tool in studies of hepatic drug metabolism and disposition. In this study, the expression and activity of drug transporters in human and rat fresh and cryopreserved hepatocytes was investigated. In human cryopreserved hepatocytes, Western blot analysis indicated that protein expression of the drug uptake transporters [human Na(+)-taurocho...

The effects of different concentrations of the hydroalcoholic extract of dried powdered leaves of Cichorium intybus L., on CCl4-induced hepatotoxicity in vivo in rats and CCl4-induced cytotoxicity in isolated rat hepatocytes were investigated. Rats received different concentrations of the extract by i.p. injection for 3 consecutive days before the injection of (3ml/kg) CCl4 (i.p.). Twenty four ...

     It has been proposed that organic nitrates such as glyceryl trinitrate (GTN), used in the treatment of cardiovascular diseases, act by producing nitric oxide (NO). However, the biochemical pathway for NO formation from GTN is not well understood. In the present study, we showed that nitrate formation from GTN, by isolated rat hepatocytes, was inhibited about 50% when cellular glutathione w...

Primary rat hepatocytes are a widely used experimental model to estimate drug metabolism and toxicity. In currently used two-dimensional (2D) cell culture systems, typical problems like morphological changes and the loss of liver cell-specific functions occur. We hypothesize that the use of polymer scaffolds could overcome these problems and support the establishment of three-dimensional (3D) c...

The release of glucokinase (hexokinase IV) from digitonin-permeabilized hepatocytes from rat, guinea pig or mouse liver is inhibited by physiological concentrations of Mg2+ (> 0.25 mM). Preincubation of hepatocytes with fructose increases glucokinase release during permeabilization in the presence of Mg2+ but decreases glucokinase release in the absence of Mg2+, suggesting that fructose causes ...