Tight Junctions In Caco-2 Cell Monolayers Research Articles

Fatty acids increase paracellular absorption of aluminium across Caco-2 cell monolayers

Passive paracellular absorption, regulated by tight junctions (TJs), is the main route for absorption of poorly absorbed hydrophilic substances. Surface active substances, such as fatty acids, may enhance absorption of these substances by affecting the integrity of TJ and increasing the permeability. It has been suggested that aluminium (Al) absorption occurs mainly by the paracellular route. Herein, we investigated if physiologically relevant exposures of fully differentiated Caco-2 cell monolayers to oleic acid and docosahexaenoic acid (DHA), which are fatty acids common in food, increase absorption of Al and the paracellular marker mannitol. In an Al toxicity test, mannitol and Al absorption through Caco-2 cell monolayers were similarly modulated by Al concentrations between 1 and 30 mM, suggesting that absorption of the two compounds occurred via the same pathways. Exposure of Caco-2 cell monolayers to non-toxic concentrations of Al (2 mM) and 14C-mannitol in fatty acid emulsions (15 and 30 mM oleic acid, 5 and 10 mM DHA) caused a decreased transepithelial electrical resistance (TEER). Concomitantly, fractional absorption of Al and mannitol, expressed as percentage of apical Al and mannitol retrieved at the basolateral side, increased with increasing dose of fatty acids. Transmission electron microscopy was applied to assess the effect of oleic acid on the morphology of TJ. It was shown that oleic acid caused a less structured morphology of TJ in Caco-2 cell monolayers. Taken together our findings indicate that fatty acids common in food increase the paracellular intestinal absorption of Al. These findings may influence future risk assessment of human Al exposure.

Novel nanoparticles for oral insulin delivery via the paracellular pathway

Novel nanoparticles (NPs) coated with chitosan which allow insulin to be administeredorally were developed. The NPs could transiently and reversibly open the tight junctions inCaco-2 cell monolayers, thus increasing their paracellular permeability. After oraladministration of the FITC-labelled NPs, fluorescence signals, co-localized with ZO-1proteins, were observed at cell–cell contact sites in the small intestine of rats. The intensityof fluorescence signals observed at the duodenum was stronger and appeared at adeeper level than at the jejunum and the ileum. The insulin-loaded NPs suspendedin water were stable in typical storage conditions. Release of the loaded insulindepended greatly on the stability of the NPs at distinct pH environments. Oraladministration of insulin in the form of NPs in diabetic rats demonstrated asustained effect of decreasing the blood glucose level over at least 10 h, indicating theeffect of the prepared NPs in enhancing the absorption of fully functional insulin.