“…For the in vitro experiments, DMSO was used as a biocompatible solvent for the poorly water-soluble APAP, but several cellular and pharmacological actions of DMSO have been described [55]. The ability of DMSO to protect cell membrane integrity is well documented [56]. Because of its effects on membrane penetration, membrane transport, and enhancement or reduction of effectiveness of other drugs, DMSO side effects and interactions with the APAP effects cannot be excluded.…”
Background/Aims: Acetaminophen (APAP) effects on intestinal barrier properties are less investigated. APAP may lead to a changed bioavailability of a subsequently administered drug or diet in the body. We investigated the influence of APAP on enterocytic cell membrane properties that are able to modify the net intestinal absorption of administered substances across the Caco-2 barrier model. Methods: The effect of APAP on cytotoxicity was measured by LDH assay, TER value and cell capacitance label-free using impedance monitoring, membrane permeability by FITC-dextrans, and efflux transporter MDR1 activity by Rh123. APAP levels were determined by HPLC analysis. Cell membrane topography and microvilli were investigated using SEM and intestinal alkaline phosphatase (Alpi) and tight junction protein 1 (TJP1) expression by western blot analysis. Results: APAP changed the apical cell surface, reduced the number of microvilli and protein expression of Alpi as a brush border marker and TJP1, increased the membrane integrity and concurrently decreased cell capacitance over time. In addition, APAP decreased the permeability to small molecules and increased the efflux transporter activity, MDR1. Conclusion: APAP alters the Caco-2 cell membrane properties by different mechanisms and reduces the permeability to administered substances. These findings may help to optimize therapeutic implications.
“…For the in vitro experiments, DMSO was used as a biocompatible solvent for the poorly water-soluble APAP, but several cellular and pharmacological actions of DMSO have been described [55]. The ability of DMSO to protect cell membrane integrity is well documented [56]. Because of its effects on membrane penetration, membrane transport, and enhancement or reduction of effectiveness of other drugs, DMSO side effects and interactions with the APAP effects cannot be excluded.…”
Background/Aims: Acetaminophen (APAP) effects on intestinal barrier properties are less investigated. APAP may lead to a changed bioavailability of a subsequently administered drug or diet in the body. We investigated the influence of APAP on enterocytic cell membrane properties that are able to modify the net intestinal absorption of administered substances across the Caco-2 barrier model. Methods: The effect of APAP on cytotoxicity was measured by LDH assay, TER value and cell capacitance label-free using impedance monitoring, membrane permeability by FITC-dextrans, and efflux transporter MDR1 activity by Rh123. APAP levels were determined by HPLC analysis. Cell membrane topography and microvilli were investigated using SEM and intestinal alkaline phosphatase (Alpi) and tight junction protein 1 (TJP1) expression by western blot analysis. Results: APAP changed the apical cell surface, reduced the number of microvilli and protein expression of Alpi as a brush border marker and TJP1, increased the membrane integrity and concurrently decreased cell capacitance over time. In addition, APAP decreased the permeability to small molecules and increased the efflux transporter activity, MDR1. Conclusion: APAP alters the Caco-2 cell membrane properties by different mechanisms and reduces the permeability to administered substances. These findings may help to optimize therapeutic implications.
“…After anesthesia with tricainemethane sulfonate, MS222 (Sandoz Pharmaceutical; East Hanover, NJ) added to the water at the concentration of 0.3 g/liter and abdominal incision, the two retia on the swimbladder wall were exposed and fixed by perfusion through the pre-retal artery with 1% glutaraldehyde in 0.1 M phosphate buffer with or without 2% acrolein and 5% DMSO (Bendayan et al 1974Sandborn et al 1975). The perfusion fixation was carried out for at least 10 min.…”
SUMMARYThe arterial endothelial cells of the rete capillaries of the eel were examined by transmission electron microscopy on thin sections, on freeze-fracture replicas, by scanning electron microscopy, after cytochemical osmium impregnation and perfusion with peroxidase. The study revealed the existence of membrane-bound tubules and vesicles that open at both the luminal and abluminal poles of the cell and at the level of the intercellular space. The tubules are straight or present successive dilations and constrictions. They branch in various directions and intrude deeply into the cell cytoplasm, forming a complex tubular network within the cell. Immunocytochemical techniques were applied on immersion-fixed tissues and on perfusion of the capillaries with albumin and insulin. These demonstrated that the tubular-vesicular system is involved in the transport of circulating proteins. Furthermore, protein A-gold immunocytochemistry has revealed the association of actin with the membranes of this system. On the basis of these results, we suggest that the transendothelial transport of serum proteins takes place by a transcytotic process through a membrane-bound tubular-vesicular system and is equivalent to the large pore system presumed from functional studies. (J Histochem Cytochem 45:1365-1378, 1997)
“…This pathway would consist of the absorption of lipase and amylase by the intestinal mucosa followed by transcytosis through the enterocyte to reach the intestinal subepithelial space. The capability of intestinal enterocytes to absorb and transport intact macromolecules has been considered as the characteristic of the intestinal tissue of embryo and newborn (Sandborn et al 1975;Udall et al 1981). It is also a characteristic of pathologies affecting the digestive tissue integrity (Weiner 1988).…”
S U M M A R Y As early as the beginning of the twentieth century some data indicated that macromolecules are able to cross the intestinal mucosa to reach the blood. Further evidence was added over the years; however, pathways for this transport still remain to be established. We report here the transfer of two pancreatic enzymes, amylase and lipase, from the intestinal lumen to the blood. Both are present in higher concentrations in the intestinal mucosa and in blood of fed rats. Upon cholinergic stimulation of pancreatic secretion, there was not only an increase in blood enzyme concentrations, but evidence for internalization by duodenal enterocytes was obtained. Following insertion of fluorochrome-tagged amylase and lipase into the duodenal lumen of fasting rats, blood and intestinal tissues were sampled at different time points. Serum activities for both enzymes clearly increased with time. Light microscopy established internalization of both proteins by duodenal enterocytes, and immunogold outlined the pathway taken by both proteins across the enterocytes. From the intestinal lumen, enzymes are channeled through the endosomal compartment to the Golgi apparatus and to the basolateral membrane reaching the interstitial space and blood circulation. Transcytosis through the intestinal mucosa thereby represents an access route for pancreatic enzymes to reach blood circulation. (J Histochem Cytochem 54:781-794, 2006)
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