Tumorigenesis caused by the peroxisome proliferator (PP) class of non-genotoxic hepatocarcinogens is species restricted; rat and mouse are considered responsive whereas the available evidence suggests that humans, non-human primates, dogs, hamsters and guinea pigs are non-responsive. We have demonstrated previously that the PP, nafenopin can suppress rat hepatocyte apoptosis both in vitro and i...

The mixed-function-oxidase (MFO) activities, ethoxyresorufin and pentoxyphenoxazone O-dealkylase, of cultured Hooded-Lister(HL)-rat hepatocytes declined rapidly during 72 h of culture, whereas in Sprague-Dawley(SD)-rat hepatocytes the MFO activities increased between 24 and 72 h in culture. Cytochrome P-450 content declined at the same rate in both HL- and SD-rat hepatocyte cultures. NADPH:cyto...

Oxidative stress has been associated with valproic acid (VPA) treatment, and mitochondrial dysfunction has been implicated in the pathogenesis of VPA-idiosyncratic hepatotoxicity. The present study investigated the effect of VPA and the role of GSH on oxidative stress, mitochondrial membrane potential, and toxicity in freshly isolated rat hepatocytes. Hepatocytes were isolated from Sprague-Dawl...

Induction of cytochromes P450 (P450s) by drugs can lead to drug-drug interactions. Primary hepatocytes have been reported to retain inducible P450s. To optimize the use of primary hepatocytes for predicting induction of P450 (CYP 3A and 2B) expression in vivo, both culture conditions and expression of induction potentials were investigated. In rat hepatocytes, basal CYP 3A1/2 expression was bet...

We investigated hepatic in vitro intrinsic clearance (CL(int,in vitro)) in freshly isolated or cryopreserved hepatocytes and compared with CL(int,in vivo) by using nine model compounds, FK1052, FK480, diazepam, diltiazem, troglitazone, quinotolast, FK079, zidovudine, and acetaminophen, in rats and humans. The compounds showed a broad range of in vivo hepatic extraction ratios (rat, 0.05-0.93; h...

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 cryoprotectiv...

BACKGROUND AND AIM Green fluorescent protein (GFP) is a widely used molecular tag to trace transplanted cells in rodent liver injury models. The differing results from various previously reported studies using GFP could be attributed to the immunogenicity of GFP. METHODS Hepatocytes were obtained from GFP-expressing transgenic (Tg) Lewis rats and were transplanted into the livers of wild-type...

Carboxylic acid-containing nonsteroidal anti-inflammatory drugs (NSAIDs) can be metabolized to chemically reactive acyl glucuronide and/or S-acyl-CoA thioester metabolites capable of transacylating GSH. We investigated the metabolism of the NSAID mefenamic acid (MFA) to metabolites that transacylate GSH, leading to MFA-S-acyl-GSH thioester (MFA-SG) formation in incubations with rat and human he...

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 was de...

Chronic consumption of the nonsteroidal anti-inflammatory drug diclofenac may induce drug-induced liver injury (DILI). The mechanism diclofenac-induced is partially elucidated and involves mitochondrial damage. Elevated cAMP protects hepatocytes against bile acid–induced injury. However, it unknown whether DILI and, if so, which downstream targets are implicated in protective mechanism, includi...