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The toxicokinetics cell demography model to explain metal kinetics in terrestrial invertebrates.

Argasinski K, Bednarska A, Laskowski R - Ecotoxicology (2012)

Bottom Line: At low constant toxicant concentrations in food, the model predicts that toxicant-driven cell mortality is moderate and the total amount of toxicant in the intestine increases slowly up to the level resulting from the gradual increase of the cell replacement rate.The increased cell death rate results in reduced toxicant absorption, which in turn brings its body load down.The resulting pattern of toxicokinetic trajectory for high metal concentration closely resemble that found in empirical studies, indicating that the model probably describes the actual phenomenon.

View Article: PubMed Central - PubMed

Affiliation: Institute of Environmental Sciences, Jagiellonian University, Gronostajowa 7, 30-387, Kraków, Poland. argas1@wp.pl

ABSTRACT
Metal toxicokinetics in invertebrates are usually described by one-compartment first-order kinetic model. Although the model gives an adequate description of the toxicokinetics in certain cases, it has been shown to fail in some situations. It also does not seem acceptable on purely theoretical grounds as accumulation and excretion rates may change depending on instantaneous toxicant concentration in the gut. We postulate that the mechanism behind such changes is connected with the toxic effect of metals on gut epithelial cells. Based on published data, we have constructed a mechanistic model assuming a dynamic rate of replacement of epithelial cells with increasing contamination. We use a population-type modeling, with a population of gut epithelial cells characterized by specific death and birth rates, which may change depending on the metal concentration in food. The model shows that the equilibrium concentration of a toxicant in an organism is the net result of gut cell death and replacement rates. At low constant toxicant concentrations in food, the model predicts that toxicant-driven cell mortality is moderate and the total amount of toxicant in the intestine increases slowly up to the level resulting from the gradual increase of the cell replacement rate. At high constant concentration, total toxicant amount in the gut increases very fast, what is accompanied by massive cell death. The increased cell death rate results in reduced toxicant absorption, which in turn brings its body load down. The resulting pattern of toxicokinetic trajectory for high metal concentration closely resemble that found in empirical studies, indicating that the model probably describes the actual phenomenon.

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Trajectory of instantaneous elimination rate (upper panel) and underlying evolution of intestine state as described by changes of contamination class sizes (lower panel, class 1 described healthy cells and next classes are more contaminated). Plotted for conditions from Fig. 3
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Fig4: Trajectory of instantaneous elimination rate (upper panel) and underlying evolution of intestine state as described by changes of contamination class sizes (lower panel, class 1 described healthy cells and next classes are more contaminated). Plotted for conditions from Fig. 3

Mentions: Therefore it is not a constant but a nonlinear function independent of intestine size, but it depends on the current state of the intestine as described by the relative sizes of contamination classes qi. Figure 4 shows the trajectory of the elimination rate and the underlying evolution of the intestine’s state (changes of sizes of contamination classes). The trajectory of the elimination rate starts at 0.11, which is the death rate in the second contamination class (the lowest class where toxins are present in the organism), and increases until the state of the intestine reaches equilibrium. Now it is clear that classical theory can be regarded as the case of a single contamination class. In this case, however, there is no neutral cell mortality and in effect no cell turnover (in the TKCD model the death probability in the last contamination class is equal to one to induce turnover). Cells in living organisms are complex objects with specific life cycles and cannot be characterized by a half-life as radioactive particles are in isotopic tracer kinetics. The TKCD model makes it clear that the assumption of linearity of transport is not defensible.Fig. 4


The toxicokinetics cell demography model to explain metal kinetics in terrestrial invertebrates.

Argasinski K, Bednarska A, Laskowski R - Ecotoxicology (2012)

Trajectory of instantaneous elimination rate (upper panel) and underlying evolution of intestine state as described by changes of contamination class sizes (lower panel, class 1 described healthy cells and next classes are more contaminated). Plotted for conditions from Fig. 3
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475973&req=5

Fig4: Trajectory of instantaneous elimination rate (upper panel) and underlying evolution of intestine state as described by changes of contamination class sizes (lower panel, class 1 described healthy cells and next classes are more contaminated). Plotted for conditions from Fig. 3
Mentions: Therefore it is not a constant but a nonlinear function independent of intestine size, but it depends on the current state of the intestine as described by the relative sizes of contamination classes qi. Figure 4 shows the trajectory of the elimination rate and the underlying evolution of the intestine’s state (changes of sizes of contamination classes). The trajectory of the elimination rate starts at 0.11, which is the death rate in the second contamination class (the lowest class where toxins are present in the organism), and increases until the state of the intestine reaches equilibrium. Now it is clear that classical theory can be regarded as the case of a single contamination class. In this case, however, there is no neutral cell mortality and in effect no cell turnover (in the TKCD model the death probability in the last contamination class is equal to one to induce turnover). Cells in living organisms are complex objects with specific life cycles and cannot be characterized by a half-life as radioactive particles are in isotopic tracer kinetics. The TKCD model makes it clear that the assumption of linearity of transport is not defensible.Fig. 4

Bottom Line: At low constant toxicant concentrations in food, the model predicts that toxicant-driven cell mortality is moderate and the total amount of toxicant in the intestine increases slowly up to the level resulting from the gradual increase of the cell replacement rate.The increased cell death rate results in reduced toxicant absorption, which in turn brings its body load down.The resulting pattern of toxicokinetic trajectory for high metal concentration closely resemble that found in empirical studies, indicating that the model probably describes the actual phenomenon.

View Article: PubMed Central - PubMed

Affiliation: Institute of Environmental Sciences, Jagiellonian University, Gronostajowa 7, 30-387, Kraków, Poland. argas1@wp.pl

ABSTRACT
Metal toxicokinetics in invertebrates are usually described by one-compartment first-order kinetic model. Although the model gives an adequate description of the toxicokinetics in certain cases, it has been shown to fail in some situations. It also does not seem acceptable on purely theoretical grounds as accumulation and excretion rates may change depending on instantaneous toxicant concentration in the gut. We postulate that the mechanism behind such changes is connected with the toxic effect of metals on gut epithelial cells. Based on published data, we have constructed a mechanistic model assuming a dynamic rate of replacement of epithelial cells with increasing contamination. We use a population-type modeling, with a population of gut epithelial cells characterized by specific death and birth rates, which may change depending on the metal concentration in food. The model shows that the equilibrium concentration of a toxicant in an organism is the net result of gut cell death and replacement rates. At low constant toxicant concentrations in food, the model predicts that toxicant-driven cell mortality is moderate and the total amount of toxicant in the intestine increases slowly up to the level resulting from the gradual increase of the cell replacement rate. At high constant concentration, total toxicant amount in the gut increases very fast, what is accompanied by massive cell death. The increased cell death rate results in reduced toxicant absorption, which in turn brings its body load down. The resulting pattern of toxicokinetic trajectory for high metal concentration closely resemble that found in empirical studies, indicating that the model probably describes the actual phenomenon.

Show MeSH
Related in: MedlinePlus