The correlations between Caco-2 permeability (logPapp) and molecular properties have been investigated. A training set of 77 structurally diverse organic molecules was used to construct significant QSAR models for Caco-2 cell permeation. Cellular permeation was found to depend primarily upon experimental distribution coefficient (logD) at pH = 7.4, high charged polar surface area (HCPSA), and r...

The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-alpha) on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell microporous filters and treated with TNF-alpha (10 or 100 ng/mL) for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux r...

the uptake and transport of 9-nitrocamptothecin (9-nc), a potent anticancer agent, across caco-2 cell monolayers was studied as a free and plga nanoparticle loaded drug. different sizes (110 to 950 nm) of 9-nitrocamptothecin nanoparticles using poly (lactic-glycolic acid) were prepared by via the nanoprecipitation method. the transport of nanoparticles across the caco-2 cell monolayer as a func...

In arid and semi-arid lands, people eats many kinds of spices. Capsaicin is one effect active component of spices. Previously we demonstrated that capsaicin induced tight junction (TJ) opening in human intestinal Caco-2 cells. We showed that the increase of TJ permeability was involved in actin polymerization. However the underlying mechanisms are unclear. The major aims of this study were to d...

The tripeptide amide glycyl-prolyl-glycinamide (GPG-amide) is a new antiretroviral drug candidate, but its absorption mechanism is unknown. In this investigation, the transport and metabolism of GPG-amide were studied in a model of the human intestinal epithelium, Caco-2 cell monolayers. The results show that when the tripeptide amide came into contact with the apical enterocyte membrane, it wa...

Mycophenolic acid (MPA) is prescribed to prevent allograft rejection in organ transplanted patients. However, its use is sporadically linked to leak flux diarrhea and other gastrointestinal (GI) disturbances in around 75% of patients through yet unknown mechanisms. Recently, we identified Midkine as a modulator of tight junctions (TJs) permeability in MPA treated Caco-2 monolayer. In the presen...

Physiologically relevant sources of absorptive intestinal epithelial cells are crucial for human drug transport studies. Human adenocarcinoma-derived intestinal cell lines, such as Caco-2, offer conveniences of easy culture maintenance and scalability, but do not fully recapitulate in vivo intestinal phenotypes. Additional sources of renewable physiologically relevant human intestinal cells wou...

BACKGROUND AND AIMS Elevated intestinal permeability of lipopolysaccharide (LPS) is a major complication for patients with parenteral nutrition (PN), but the pathogenesis is poorly understood. Intestinal P-glycoprotein (P-gp) is one of the efflux transporters that contribute to restricting the permeability of lipopolysaccharide via transcellular route. P-gp expression may be regulated by PN ing...

Previous studies have shown that high concentrations of ethanol (≥40%) cause functional damage of the gastrointestinal epithelial barrier by direct cytotoxic effect on the epithelial cells. The effects of lower noncytotoxic doses of ethanol on epithelial barrier function are unknown. A major function of gastrointestinal epithelial cells is to provide a barrier against the hostile substances in ...

To investigate the effect of autophagy on claudin-2 in lipopolysaccharide (LPS) induced hyper-permeability of intestinal epithelial cell. In human colon cancer cell line (Caco-2), the model of intestinal epithelial injury induced by LPS was established, which were LPS group, LPS combined with inhibitor of autophagy (3-Methyladenine, 3-MA) and control group. Transepithelial resistance (TER) was ...