0035 μmol/l blood or from 0 to 0 4 μmol/l blood (rats), blood of

0035 μmol/l blood or from 0 to 0.4 μmol/l blood (rats), blood of naïve animals (about 30 mice or 10 rats) was pooled. Blood samples were treated as described under Section 2.3 with the difference that between 5 and 20 μl of an acetonic solution

of a predefined concentration of racemic DEB was added into the samples before the preparation of plasma. In total, four calibration curves were constructed for mice and eight calibration curves for rats. Linear regression analyses revealed coefficients of determination (R2) of between 0.992 and 0.999. The limits of detection of DEB (3 times the background selleck inhibitor noise) were 1 nmol/l (mouse blood) and 0.3 nmol/l (rat blood). Fig. 2 shows (±)-DEB and meso-DEB in the blood of BD exposed mice ( Fig. 2A and a) and rats ( Fig.

2B and b). All measured data are given in Fig. 2A and B, excerpts demonstrating DEB concentrations at low BD exposure concentrations of between 0 and 21 ppm are given in Fig. 2a and b. Large standard errors are seen in rats. The individual rat data may reflect the fact that DEB Stem Cell Compound Library is only a minor second-order BD metabolite in the rat liver ( Filser et al., 2010). In mice, the figure shows only small differences in the means of two groups of 6 animals each, both of which were exposed identically. In non-exposed control animals of both species, there was no DEB background. Also no DEB-related background was found by Georgieva et al. (2010) who investigated DEB-characteristic adducts at the N-terminal valine of hemoglobin (N,N-(2,3-dihydroxy-1,4-butadiyl)-valine)

in mice and rats repeatedly exposed over 2 weeks to BD concentrations of between 0 and 625 ppm. In mice, measured (±)-DEB blood concentrations seem to reach a plateau concentration of about 1.74 μmol/l at 600 ppm BD. In rat blood, mean concentrations of (±)-DEB amount to not more than 0.1 μmol/l. Of this concentration, 70% is reached at 100 ppm BD. The curves, also shown in the figure, were fitted to the data by means of Prism 5 for Mac OS X (GraphPad Software, La Jolla, California) using one-phase exponential association functions. These functions were preferred to Michaelis–Menten functions because they provided higher correlation coefficients. The (±)-DEB blood concentrations in mice, calculated by means of the one-phase exponential association function, increased L-gulonolactone oxidase from 5.4 nmol/l at 1 ppm BD to 1860 nmol/l at 1250 ppm BD. In rats, they increased from 1.2 nmol/l at 1 ppm BD to 92 nmol/l at 200 ppm BD. At this exposure concentration, 91% of the calculated DEB plateau concentration in rat blood was reached. In both species, the blood concentrations of the (±) form are much higher than those of the meso form. The ratio of (±)- to meso-DEB is similar in mice and rats and does not change very much in the whole exposure range. It is between 21 and 32 in mouse blood and between 17 and 21 in rat blood. Goggin et al.

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