Caco-2 cells intestinal

Cell culture Damage to small intestinal epithelial cells by XO can be prevented by SOD and desferrioxamine (Ma et al., 1991), whilst that to rat enterocytes, CaCo cells or rabbit colonic epithelial cells by XO can be decreased by catalase (Baker and Baker, 1990 Baker and Campbell, 1991 Kawabe etal., 1992). 

O Sullivan, L, Ryan, L, and O Brien, N, 2007. Comparison of the uptake and secretion of carotene and xanthophyll carotenoids by Caco-2 intestinal cells. Br J Nutr 98, 38 -4. 

The Human Caco-2 Intestinal Cell Model A Valuable Tool for Studying Carotenoid... 

THE HUMAN CACO-2 INTESTINAL CELL MODEL A VALUABLE TOOL FOR STUDYING CAROTENOID ABSORPTION... 

The solutes for which transport was evaluated in the IPL were also assayed for their transport in epithelial cell culture models. Permeability in the Caco-2 intestinal cell culture model [141] and the 16HBE14o- airway cell culture model [81] correlated with the rate of absorption in the IPL, with correlation coefficients of r = 0.96 and r2 = 0.78 respectively. 

Halleux C Schneider YJ (1991) Iron absorption by intestinal epithelial cells 1. CaCO, cells cultivated in serum-free... 

Intestine/colon cancer cells The caco-2 intestinal cell monolayer is a good model for testing permeability and oral deliverability of compounds [39]. 

Huang N, Wu GD. Short chain fatty acids inhibit the expression of the neutrophil chemoattractant, interleukin 8, in the Caco-2 intestinal cell line. Adv Bxp Med Biol 1997 427 145-153. 

ADME is now a routine part of the efforts of a drug discovery team with the use of a number of in vitro approaches, e.g., Caco 2 intestinal cell lines (144,145), human liver slices, or homogenates to assess potential metabolic pathways (119), in addition to classical rat, dog, and nonhuman primate in vivo studies, none of which has yet shown reliable predictability for the human situation. More recently, the use of proteomics to derive potential toxicological profiles has been assessed (146) as has increasing the throughput of compound evaluation in conjunction with increased computational support (147). 

An anomalously high efficacy is usually the result of the action of a protein transporter or endocytotic mechanism. Biological membranes contain protein components evolved specifically for transporting hydrophilic nutrients across the membrane. Cellular models that directly measure permeability from both passive diffusion and transport mechanisms have been developed for screening purposes using monolayers of Caco-2 intestinal adenocarcinoma cells or MDK canine kidney cells. 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

Artursson P and Karlsson J. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochem Biophys Res Commun 1991 175 880-5. 

Snyder NJ, Tabas LB, Berry DM, Duckworth DC, Spry DO and Dantzig AH. Structure-activity relationship of carbacephalosporins and cephalosporins antibacterial activity and interaction with the intestinal proton-dependent dipeptide transport carrier of Caco-2 cells. Antimicrob Agents Chemother 1997 41 1649-57. 

LIU Y and HU m (2002) Absorption and metabolism of flavonoids in the caco-2 cell culture model and a perfused rat intestinal model. Drug Metab Dispos. 30 (4) 370-77. 

In culture, the human colon carcinoma cell hne Caco-2 spontaneously differentiates at confluency into polarized cells with enterocyte-like characteristics. The principle of this approach consists of following the passage of the compound of interest from the apical or lumen-like sides to the basolateral or lymph-hke sides of Caco-2 cells, thus following the absorption of the compound per se. One obhgate step for fat-soluble nutrients such as carotenoids to cross the intestinal barrier is their incorporation into CMs assembled in the enterocytes. Under normal cell culture conditions, Caco-2 cells are unable to form CMs. When supplemented with taurocholate and oleic acid, Caco-2 cells were reported to assemble and secrete CMs. ... 

In contrast to previous in vivo models, this in vitro model provides the possibility of dissociating experimentally two important processes of intestinal absorption cellular uptake and secretion. Under conditions mimicking the postprandial state (taurocholate/oleic acid supplementation), differentiated Caco-2 cells were able to (1) take up carotenoids at the apical sides and incorporate them into CMs and (2) secrete them at the basolateral sides associated with CM fractions. Using this approach, the extent of absorption of P-carotene through Caco-2 cell monolayers after 16 hr of incubation was 11.2%, a value falling within the in vivo range (9 to 22%). ° - Of the total amount of P-carotene secreted, 78% was associated with the two CM fractions and 10% with the VLDL fraction. ... 

This in vitro approach thus has a great potential for studying the intestinal absorption processes of carotenoids and other pigments. It is important to note the existence of several clones isolated from the parent Caco-2 cell line that can be used for studying... 

During, A., Albaugh, G., and Smith, J.C., Characterization of 3-carotene 15,15-dioxygenase activity in TC7 clone of human intestinal cell line Caco-2 cells, Biochem. Biophys. Res. Commun., 249, 467, 1998. 

Salvini, S. et al.. Functional characterization of three clones of the human intestinal Caco-2 cell hne for dietary lipid processing, Br. J. Nutr., 87, 211, 2002. 

Ferruzzi, M.G., Failla, M.L., and Schwartz, S.J., Assessment of degradation and intestinal cell uptake of carotenoids and chlorophyll derivatives from spinach puree using an in vitro digestion and Caco-2 cell model, J. Agric. Food Chem., 49, 2082, 2001. 

Chitchumroonchokchai, C., Schwartz, S.J., and Failla, M.L., Assessment of lutein bioavailability from meals and a supplement using simulated digestion and Caco-2 human intestinal cells, J. Nutr, 134, 2280, 2004. 

Since experimental determination of intestinal absorption is quite demanding, Caco-2 cell monolayers have been successfully used to model passive drug absorption. Several models for the prediction of Caco-2 permeability using PSA were developed, including those of van de Waterbeemd et al. [5] and Palm et al. [22] who found that relationships between Caco-2 permeability and PSA is stronger than with Clog D, Krarup et al. [23] who used dynamic PSA calculated for water accessible molecular surface and Bergstrom et al. [24]. 

Yamashita, S. Furubayashi, T. Kataoka, M. Sakane, T. Sezaki, H. Tokuda, H., Optimized conditions for prediction of intestinal drug permeability using Caco-2 cells, Eur. J. Pharm. Sci. 10, 109-204 (2000). 

Artursson, R, Epithelial transport of drugs in cell culture. I A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells, J. Pharm. Sci. 79, 476-482 (1990). 

Karlsson, J. P. Artursson, P., A method for the determination of cellular permeability coefficients and aqueous boundary layer thickness in monolayers of intestinal epithelial (Caco-2) cells grown in permeable filter chambers, Int. J. Pharm. 7, 55-64 (1991). 

Hilgers, A. R. Conradi, R. A. Burton, P. S., Caco-2 cell monolayers as a model for drug transport across the intestinal mucosa, Pharm. Res. 7, 902-910 (1990). 

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