Uptake of xenobiotics

The major routes of uptake of xenobiotics by animals and plants are discussed in Chapter 4, Section 4.1. With animals, there is an important distinction between terrestrial species, on the one hand, and aquatic invertebrates and fish on the other. The latter readily absorb many xenobiotics directly from ambient water or sediment across permeable respiratory surfaces (e.g., gills). Some amphibia (e.g., frogs) readily absorb such compounds across permeable skin. By contrast, many aquatic vertebrates, such as whales and seabirds, absorb little by this route. In lung-breathing organisms, direct absorption from water across exposed respiratory membranes is not an important route of uptake. 

Although the radioactive isotope H has been extensively used for studies on the uptake of xenobiotics into whole cells, the intrusion of exchange reactions and the large isotope effect renders this isotope rather less straightforward for metabolic studies. Both deuterium H-labeled substrates, and oxygen and OH2 have, however, been extensively used in metabolic studies, since essentially pure labeled compounds are readily available and mass spectrometer facilities have become an essential part of structural determination. 

Bioaccumulation is defined as the uptake of xenobiotics and their retention by living organisms. Bioconcentration is the term applied to the uptake and retention of xenobiotics by organisms from their immediate environment. Biomagnification is the term applied to uptake and retention of xenobiotics from food. 

Trapp, S., C. McFarlane, and M. Matthies. 1994. Model for Uptake of Xenobiotics into Plants Validation with Bromadl Experiments. Environ. Toxicol. Chem. 13, 413-422. 

Toxicokinetics Quantitative uptake of xenobiotics by the body, its biotransformation, distribution, metabolism, and elimination from the body. 

The slope of the curve corresponds to 7 A. In most experimental setups, the surface area A is known and flux J can be derived. Constant flux is maintained as long as C/j is much larger than Ca and as long as both are practically unchanged. In biologic systems, a good example for such conditions may be the uptake of xenobiotics from the Gl-tract, where the GI tract acts as a reservoir for the molecules, which are transported through the intestinal epithelium into the blood, which acts as a sink. 

Proximal tubule cells in culture should have retained functional attributes such as (1) polar architecture and junctional assembly of epithelia and correct membrane distribution of enzymes and transport systems (2) vectorial transport of solutes and water, manifested by the formation of domes when cultured on solid supports [81] and the generation of transepithelial electrophysiological properties [82, 83] due to the expression of proximal tubule specific claudins 2- and 10 [84, 85] (3) cellular uptake of xenobiotics from either the apical or basolateral side, as observed in vivo and (4) expression of nephron segment-specific characteristics, i.e., distinct expression of differentiation markers, metabolic and transport properties, and hormone responsiveness. Such markers include the expression of the brush border enzymes alkaline phosphatase, leucine aminopeptidase, and y-glutamyl transferase [4, 86], In addition, proximal tubule cells should possess Na+,K+-ATPase activities, Na+-dependent glucose, and p-aminohippurate transport. Proximal tubule cells increase cAMP levels in response to parathyroid... 

Biliary excretion represents another important route for the elimination of drugs and other xenobiotics. Following the uptake of xenobiotics into the hepatocytes, compounds may undergo metabolic modification, or the parent compound, as... 

Partitioning into Biota Uptake of Xenobiotics from the Aqueous Phase... 

The uptake of xenobiotics by a range of agricultural plants including barley, lettuce, carrots, and radish illustrated the different modes of uptake and translocation (Schroll et al. 1994). 

Care should therefore be exercised in extrapolation of the results from all surrogate methods to assessing the uptake of xenobiotics into natural biota from the water phase. 

Iannuzzi T.J., Harrington N.W., Shear N.M., Curry C.L., Carson-Lynch H., Henning M.H., Su S.H., Raabe D.E. (1996) Distribution of key exposure factors controlling the uptake of xenobiotic chemicals in an estuarine food web. Environ.Toxicol. Chem. 15, 1979—92. 

Structure Our understanding of the composition, structure, and function of biological membranes has developed rapidly in recent years. Not only do these cellular components influence uptake of nutrients, but they also play significant roles in communication between cells. In this discussion, however, the focus will be on the involvement of the membrane in the uptake of xenobiotics. The... 

The use of in vitro dermal absorption studies on isolated skin is based on the fact that the epidermis, in particular the stratum comeum, forms the principal in vivo barrier of the skin against the penetration and uptake of xenobiotics in the body. 

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