6- mercaptopurine (6-mp) is widely used in clinic as an immunosuppressive for treatment of acute lymphocytic leukemia, crohn's disease, and ulcerative colitis with documented unpredictable hepatotoxicity. the potential molecular cytotoxic mechanisms of 6-mp against isolated rat hepatocytes were searched in this study using “accelerated cytotoxicity mechanism screening (acms)” techniques. t...

Freshly isolated hepatocytes are considered the gold standard for in vitro studies of hepatic drug disposition. To ensure a reliable supply of cells, cryopreserved human hepatocytes are often used. ABC-superfamily drug efflux transporters are key elements in hepatic drug disposition. These transporters are often considered lost after isolation of hepatocytes. In the present study, the expressio...

The replicative responses of suckling and adult rat hepatocytes in primary culture to growth-stimulating factors were compared. By addition of L-proline alone, the [3H]-thymidine labeling of suckling rat hepatocytes was dramatically enhanced, but that of adult ones was not. Epidermal growth factor (EGF), insulin, triiodothyronine (T3) and glucagon also enhanced the labeling of suckling rat hepa...

Adult hepatocytes are polarised with their apical and basolateral membranes separated from neighbouring cells by tight junction proteins. Although efficient differentiation of pluripotent stem cells to hepatocytes has been achieved, the formation of proper polarisation in these cells has not been thoroughly investigated. In the present study, human embryonic stem cells (hESCs) and human mesench...

The novel approach of tissue engineering to treat many forms of liver diseases using hepatocytes requires sufficient numbers and sustained survival of the transplanted cells. It has been shown that providing extracellular matrix components extracted from Engelbreth-HolmSwarm cells (EHS-ECMs) to heterotopically transplanted hepatocytes allows significantly greater hepatocyte survival. We investi...

inclusion body hepatitis (ibh) has been reported in many countries in the world. the ibh or similar cases characterized by hepatitis and presence of intra-nuclear inclusion bodies in hepatocytes have not been reported in broiler chickens in iran. this is the first report on outbreak of adenovirus-like inclusion body hepatitis in iran. on october 2012, an onset of high acute mortality in a flock...

overdose of acetaminophen causes severe hepatic necrosis in humans and experimental animals. studies on its hepatotoxicity remain a very active area since some of current data are still uncertain. in this study, freshly isolated rat hepatocytes were used to determine the effects of garlic extract and its component, allicin on the acetaminophen-induced cell cytotoxicity and to compare with the e...

background: chemical toxins are among the leading causes of liver disorders, inflammation and necrosis in hepatocytes. the aim of this study was to evaluate of protective effect of hydroalcoholic extract from rhizome of zingiber officinale l. (hez) on carbon tetrachloride-induced hepatic injury in male rat. material and methods: in this experimental studymale wistar rats (n=35, body weight 230-...

in this research, we investigated the cytotoxic mechanisms of one of the widely used pharmaceuticals that are regularly associated with the adverse effects on the liver, sometimes leading to acute liver failure, diclofenac. diclofenac liver cytotoxicity was associated with reactive oxygen species (ros) formation and lipid peroxidation which were inhibited by antioxidants and ros scavengers, fer...

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...