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- Unité de Toxicologie Alimentaire - Dijon In vitro metabolism of DADS by rat and human subcellular fractions Results in rat presented Results in human.

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Presentation on theme: "- Unité de Toxicologie Alimentaire - Dijon In vitro metabolism of DADS by rat and human subcellular fractions Results in rat presented Results in human."— Presentation transcript:

1 - Unité de Toxicologie Alimentaire - Dijon In vitro metabolism of DADS by rat and human subcellular fractions Results in rat presented Results in human similar with the same metabolites

2 - Unité de Toxicologie Alimentaire - Dijon cofactors DADS HPLC-UV microsomes cytosols In vitro metabolism of DADS in rat ultracentrifugation subcellular fractions

3 - Unité de Toxicologie Alimentaire - Dijon DADS CYP 2B1/2 CYP 2E1 FMO AGS allyl glutathionyl sulfide AM allyl mercaptan GST DADSO

4 - Unité de Toxicologie Alimentaire - Dijon DADSO Km nmole Vmax nmol/min/mg prt Vmax/Km AGS + AM products  DADS  DADSO DADSO monooxigenase nmol/min/mg prt GST nmol/min/mg prt monooxygenase + GST nmol/min/mg prt AGS products AM 1.82 ± 0.20 6.18 ± 0.23 0.21 ± 0.01 11.00 ± 1.67 0.21 ± 0.01n.d.  DADS  DADSO + AM + AGS 0.86 ± 0.120.47 ± 0.12 9.03 ± 2.560.25 ± 0.04 1.83 0.03

5 - Unité de Toxicologie Alimentaire - Dijon Isolated rat perfused liver livercollected bile

6 - Unité de Toxicologie Alimentaire - Dijon Single dose pharmacokinetic parameters for DADS in an isolated perfused rat liver. kel (min-1) 0.13 ± 0.03 AUC0-  (min.mmol/l) 4.77 ± 0.80 t1/2 (min) 6.09 ± 1.26 Clearance (ml/min)34.22 ± 5.6 Volume of distribution (ml)311.9 ± 0.08

7 - Unité de Toxicologie Alimentaire - Dijon Total Ionic Current chromatogram of the extract of liver, perfused with DADS, obtained on GC-MS.

8 - Unité de Toxicologie Alimentaire - Dijon GST DADS AGS allyl glutathionyl sulfide AM allyl mercaptan AMS allyl methyl sulfide CYP 2B1/2 CYP 2E1 FMO AMSO2 allyl methyl sulfone AMSO allyl methyl sulfoxide DADSO Compounds obtained in presence of subcellular fractions Compounds obtained in an isolated perfused liver MT

9 - Unité de Toxicologie Alimentaire - Dijon DADS: short half live time many metabolites  Which is the real active molecule in vivo ?


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