Epithelial tissues liver hepatocytes

MRP4 is abundantly expressed in the kidney followed by the liver (238,260). The membrane localization of Mrp4 is tissue dependent sinusoidal membrane in the hepatocytes (261), brush border membrane of the renal tubules (262,263), luminal membrane of the brain capillaries (262), and basolateral membrane of the choroid epithelial cells (262). 

P-gp is constitutively expressed in nearly all barrier tissues. Techniques involving Northern blots (37) or Western blots with monoclonal antibodies such as C219 (38) and MRK 16 (39) have been used extensively to determine the tissue distribution of P-gp. It is expressed in adrenal cortex, kidney, liver, intestine, and pancreas endothelial cells at blood-tissue barriers, namely, the CNS, the testis, and in the papillary dermis (3,4,38,40,41). P-gp displays specific subcellular localization in cells with a polarized excretion or absorption function. More specifically, P-gp is found at the apical (AP) canalicular surface of hepatocytes, in the AP membrane of the columnar epithelial cells of colon and jejunum, and the AP brush border of the renal proximal tubule epithelium (3,4,40 1-2). In endothelial cells, P-gp is located in the luminal membrane (4,43). 

Stem cells are progenitor cells which are not yet specifically formed. They can multiply almost infinitely and form nearly all 210 tissue types in the human being. Depending on their derivation, they are defined as follows .) embryonal (= taken from the inner cell mass of the blastocysts), (2.) foetal (= isolated from 5-9 week-old abortive foetuses, and (5.) adult (= taken from the tissue of adults or children by means of biopsy or from the umbilical cord of newborns. Adult stem cells are limited in number and life span they do, however, have a broader development potential than so far assumed. They have also been found in the liver. The transformation of stem cells from the bone marrow into hepatocytes has been carried out successfully. Liver stem cells (7-15 gm) can develop both primary cell types of the liver, (7.) mature hepatocytes and (2.) biliary epithelial cells. These stem cells are deemed to be genuine liver stem cells, and not merely derived from the activation of immature oval cells in the liver. (54,59, 60, 81) (s. fig. 2.20)... 

The purpose of this chapter is to present overviews of a selection of the major endothelial and epithelial barriers to drug delivery for which there are either primary culture or cell line systems that recapitulate the characteristics of the in vivo barrier. Our objective is to define some general characteristics of cell culture models and highlight the more commonly applied primary cell cultures and cell lines in use today. Specifically, we focus on cell culture models for the intestinal epithelium, blood-brain barrier, pulmonary and nasal epithelium, ocular epithelium, placental barrier, and renal epithelium. Renal epithelium was included here primarily because some cell lines derived from this tissue [e.g., Madin-Darby canine kidney cells (MDCK)] are often used as surrogates for other barriers by pharmaceutical scientists. We have arbitrarily chosen to exclude the skin and liver from the scope of this overview. However, it should be noted that hepatocyte cell culture models, for example, are becoming more widely available and have been the subject of recent reviews.1,2... 

Figure 13-2 Distribution of some elements shown separately in Figure 13-1 in some known tissue compartments, int, intestine hep, hepatocytes bm, bone marrow TfR, transferrin receptors in cells in bone marrow ly, lymphocytes. Lymphocytes ( ) are shown here in the liver. They belong, however, to a pool of cells continuously recirculating between blood and lymph. This could give them a preferential capacity of surveillance of sites where non-transferrin bound iron levels might be abnormally high. Divalent cation transporters represented here by DCTl may come to have important roles in the first step of iron entry into an organism through the intestinal epithelial cells.

Fig. 32.13. Fate of chylomicrons. Chylomicrons are synthesized in intestinal epithelial cells, secreted into the lymph, pass into the blood, and become mature chylomicrons (see Fig. 32.11). On capillary walls in adipose tissue and muscle, lipoprotein lipase (LPL) activated by ApoCn digests the triacylglycerols (TG) of chylomicrons to fatty acids and glycerol. Fatty acids (FA) are oxidized in muscle or stored in adipose cells as triacylglycerols. The remnants of the chylomicrons are taken up by the liver by receptor-mediated endocytosis. Lysosomal enzymes within the hepatocyte digest the remnants, releasing the products into the cytosol.

In animal studies, when the AZA is administered per os, it caused degeneration of epithelial cells and necrosis of the lamina propria in the villi of the small intestine and in lymphoid tissues such as thymus, spleen, and the Peyer s patches fat accumulation in the liver and degeneration of hepatocytes reduction of nongranulocytes and damage to T- and B-cells in the spleen. Overall, AZAl induced a far greater degree of tissue injury and slower recovery time when compared with OA [62,63]. 

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