| Abstrakt: |
A study was conducted to investigate qualitative and quantitative aspects of the phase I metabolism of 3-methylindole (3MI) by porcine liver microsomes. Microsomal suspensions were prepared from the liver of 30 intact (uncastrated) male pigs. Metabolites produced in microsomal incubations were identified and quantitated with HPLC-UV, HPLC-fluorescence, and UV-spectral analysis; liquid chromatography-mass spectrometry (LC-MS) and NMR were used for the identification of a metabolite for which a reference compound was not available. The results showed that seven major metabolites of 3MI are produced by porcine microsomes, three of which had already been identified in pigs (3-OH-3-methyloxindole, 5-OH-3-methylindole, and 6-OH-3-methylindole). The other four major 3MI metabolites identified were 3-OH-3-methylindolenine, 3-methyloxindole, indole-3-carbinol, and 2-aminoacetophenone. On average, the metabolite that was produced in larger amounts was 3-OH-3-methylindolenine (45.1%), followed by the two oxindoles 3-methyloxindole (27.9%) and 3-OH-3-methyloxindole (18.5%). Average percentage of production of 6-OH-3-methylindole was 4.9%, whereas indole-3-carbinol accounted for 2.7% of all metabolites produced; 2-amino-acetophenone and 5-OH-3-methylindole were the metabolites produced in lesser amounts (0.5 and 0.3%, respectively). Large interindividual differences in the rate of production of all metabolites were observed. This variation could be attributed to differences in the activity and/or level of expression of phase I biotransformation enzymes and this issue should be further investigated. |
