CDP-840 is a selective and potent phosphodiesterase type IV inhibitor, whose in vitro metabolism profile was first investigated using liver microsomes from different species. At least 10 phase I oxidative metabolites (M1-M10) were detected in the microsomal incubations and characterized by capillary high-performance liquid chromatography continuous-flow liquid secondary ion mass spectrometry (C...

Azathioprine (AZA) is widely used in clinical practice for preventing graft rejection in organ transplantations and various autoimmune and dermatological diseases with documented unpredictable hepatotoxicity. The potential molecular cytotoxic mechanisms of AZA towards isolated rat hepatocytes were investigated in this study using "Accelerated Cytotoxicity Mechanism Screening" techniques. The co...

An isolated rat hepatocyte preparation was used to study the cellular toxicity of cadmium and the protective effects of metallothionein on cadmium-induced toxicity. Exposure of primary suspension cultures of isolated rat hepatocytes to Cd2+ (0-35.7 microM) for 15 min resulted in a dose-dependent reduction in the synthesis of cellular proteins during a subsequent 6 h incubation. Such inhibition ...

background hepatocytes are used as an in vitro model to evaluate drug metabolism. human hepatocyte transplant has been considered as the temporary treatment of acute liver failure. optimization freezing methods is very important to preserve both cell viability and function which are achieved by cryopreservation mostly always. objectives the present study aimed to investigate the cryoprotective ...

Incubation of isolated rat hepatocytes with oxytocin produces a time- and dose-dependent inactivation of glycogen synthase. Such inactivation is associated with an increase in the phosphorylation state of the 88 kDa subunit of the enzyme, as observed after electrophoretic analysis of the 32P-labelled enzyme isolated by immunoprecipitation from cells incubated with [32P]phosphate. CNBr cleavage ...

Because our previous studies indicated that squalestatin 1 treatment induces CYP2B expression in primary cultures of rat hepatocytes as a direct consequence of squalene synthase inhibition, we investigated possible underlying mechanisms. Cotransfection of cultured Sprague-Dawley male rat hepatocytes with each of the three sterol regulatory element binding protein (SREBP) transcription factors f...

OBJECTIVE Liver fibrosis and subsequent cirrhosis is a major cause of death worldwide, but few effective antifibrotic therapies are reported. Whey-hydrolyzed peptide (WHP), a major peptide component of bovine milk, exerts anti-inflammatory effects in experimental models. A WHP-enriched diet is widely used for immunomodulating diets (IMD) in clinical fields. However, the effects of WHP on liver ...

A membrane fraction denoted N2 upper was isolated from homogenates of rat liver by sucrose gradient centrifugation. This fraction, which was enriched 65-fold over the homogenate in 5'-nucleotidase activity, was used as an immunogen in goats. The antisera obtained contained antibodies to three predominant polypeptides in the N2 upper membrane fraction, as shown by crossed immunoelectrophoresis. ...

The use of cultured primary hepatocytes within toxicology has proven to be a valuable tool for researchers, however, questions remain with regard to functional differences observed in these hepatocytes relative to the intact liver. Cultured hepatocytes have typically been described as dedifferentiated, a classification based upon the investigation of a few key cellular processes or hepatocellul...