Comparative metabolism of BHA, BHT and other phenolic antioxidants and its toxicological relevance

Identifying xenobiotic metabolites with in silico prediction tools and LCMS suspect screening analysis

“…Of the 33 parent compounds investigated in this study, no reported metabolites were included for 2-nitrotoluene, 3,5-dinitroaniline, butylated hydroxytoluene, or lindane. While there are studies that identify metabolites for lindane ( Fitzloff et al, 1982 ), 2-nitrotoluene ( DeBethizy and Rickert, 1984 ) and butylated hydroxytoluene ( Conning and Phillips, 1986 ), these articles were not identified by the authors prior to generation of the MS 2 spectra suspect screening library.…”

Identifying xenobiotic metabolites with in silico prediction tools and LCMS suspect screening analysis

“…Of the 33 parent compounds investigated in this study, no reported metabolites were included for 2-nitrotoluene, 3,5-dinitroaniline, butylated hydroxytoluene, or lindane. While there are studies that identify metabolites for lindane ( Fitzloff et al, 1982 ), 2-nitrotoluene ( DeBethizy and Rickert, 1984 ) and butylated hydroxytoluene ( Conning and Phillips, 1986 ), these articles were not identified by the authors prior to generation of the MS 2 spectra suspect screening library.…”

Metabolism of a Bioorthogonal PET Tracer Candidate [19F/18F]SiFA-Tetrazine in Mouse Liver Microsomes: Biotransformation Pathways and Defluorination Investigated by UHPLC-HRMS

“…The metabolism of 2,6-di- tert -butyl- p -cresol (BHT) demonstrated species-specific oxidation, with the aromatic ring bound methyl group being hydroxylated in rat, rabbit, and monkey, and tert -butyl groups in human. 50 In all the aforementioned compounds, the sp 3 -carbon was oxidized in the presence of an aromatic ring, which was left intact. This supports the hypothesis that SiFA–Tz is likely oxidized from the tert -butyl groups adjacent to the silicon atom.…”

“…Previously reported findings on the metabolism of Finasteride and Docetaxel, both compounds containing a tert -butyl group and or aromatic ring, demonstrate that the tert -butyl undergoes oxidation at one sp 3 -carbon rather than an aromatic ring. The metabolism of 2,6-di- tert -butyl- p -cresol (BHT) demonstrated species-specific oxidation, with the aromatic ring bound methyl group being hydroxylated in rat, rabbit, and monkey, and tert -butyl groups in human . In all the aforementioned compounds, the sp 3 -carbon was oxidized in the presence of an aromatic ring, which was left intact.…”

Effects of Food Constituents on Absorption and Bioaccessibility of Dietary Synthetic Phenolic Antioxidant by Caco-2 Cells

“…After a 5 h exposure, BHT-Q in the cell compartment was 7.56 ± 0.30% of the initial BHT dose and BHT-Q in apical and basolateral compartments was only 0.07 ± 0.003 and 0.04 ± 0.01%, respectively (Figure ). Oxidative metabolism (phase I reactions), mediated by a cytochrome P450 monooxygenase, is the major route for BHT transformation, and BHT activation has been ascribed to the activity of the CYP2B enzyme, which may be responsible for BHT-Q formation. , Lipid micelles can stimulate the secretion of chylomicrons (i.e., apolipoprotein B (apoB) 48-containing lipoproteins) by Caco-2 cells, and the cytochrome P450 isoenzyme can be found on the surfaces of the lipoproteins. , These may explain why metabolites were detected under the lipid state. In contrast to BHT-Q and BHT-quinol, the metabolites of the oxidation of the alkyl substituents pathway of BHT, i.e., BHT-OH, BHT-CHO, and BHT-COOH, were not detected in any of the nutrient conditions.…”

“…Oxidative metabolism (phase I reactions), mediated by a cytochrome P450 monooxygenase, is the major route for BHT transformation, and BHT activation has been ascribed to the activity of the CYP2B enzyme, which may be responsible for BHT-Q formation. 36,37 Lipid micelles can stimulate the secretion of chylomicrons (i.e., apolipoprotein B (apoB) 48containing lipoproteins) by Caco-2 cells, and the cytochrome P450 isoenzyme can be found on the surfaces of the lipoproteins. 38,39 These may explain why metabolites were detected under the lipid state.…”

Identifying xenobiotic metabolites with in silico prediction tools and LCMS suspect screening analysis

“…Of the 33 parent compounds investigated in this study, no reported metabolites were included for 2-nitrotoluene, 3,5-dinitroaniline, butylated hydroxytoluene, or lindane. While there are studies that identify metabolites for lindane ( Fitzloff et al, 1982 ), 2-nitrotoluene ( DeBethizy and Rickert, 1984 ) and butylated hydroxytoluene ( Conning and Phillips, 1986 ), these articles were not identified by the authors prior to generation of the MS 2 spectra suspect screening library.…”

Metabolism of a Bioorthogonal PET Tracer Candidate [19F/18F]SiFA-Tetrazine in Mouse Liver Microsomes: Biotransformation Pathways and Defluorination Investigated by UHPLC-HRMS

“…The metabolism of 2,6-di- tert -butyl- p -cresol (BHT) demonstrated species-specific oxidation, with the aromatic ring bound methyl group being hydroxylated in rat, rabbit, and monkey, and tert -butyl groups in human. 50 In all the aforementioned compounds, the sp 3 -carbon was oxidized in the presence of an aromatic ring, which was left intact. This supports the hypothesis that SiFA–Tz is likely oxidized from the tert -butyl groups adjacent to the silicon atom.…”

“…Previously reported findings on the metabolism of Finasteride and Docetaxel, both compounds containing a tert -butyl group and or aromatic ring, demonstrate that the tert -butyl undergoes oxidation at one sp 3 -carbon rather than an aromatic ring. The metabolism of 2,6-di- tert -butyl- p -cresol (BHT) demonstrated species-specific oxidation, with the aromatic ring bound methyl group being hydroxylated in rat, rabbit, and monkey, and tert -butyl groups in human . In all the aforementioned compounds, the sp 3 -carbon was oxidized in the presence of an aromatic ring, which was left intact.…”

Effects of Food Constituents on Absorption and Bioaccessibility of Dietary Synthetic Phenolic Antioxidant by Caco-2 Cells

“…After a 5 h exposure, BHT-Q in the cell compartment was 7.56 ± 0.30% of the initial BHT dose and BHT-Q in apical and basolateral compartments was only 0.07 ± 0.003 and 0.04 ± 0.01%, respectively (Figure ). Oxidative metabolism (phase I reactions), mediated by a cytochrome P450 monooxygenase, is the major route for BHT transformation, and BHT activation has been ascribed to the activity of the CYP2B enzyme, which may be responsible for BHT-Q formation. , Lipid micelles can stimulate the secretion of chylomicrons (i.e., apolipoprotein B (apoB) 48-containing lipoproteins) by Caco-2 cells, and the cytochrome P450 isoenzyme can be found on the surfaces of the lipoproteins. , These may explain why metabolites were detected under the lipid state. In contrast to BHT-Q and BHT-quinol, the metabolites of the oxidation of the alkyl substituents pathway of BHT, i.e., BHT-OH, BHT-CHO, and BHT-COOH, were not detected in any of the nutrient conditions.…”

“…Oxidative metabolism (phase I reactions), mediated by a cytochrome P450 monooxygenase, is the major route for BHT transformation, and BHT activation has been ascribed to the activity of the CYP2B enzyme, which may be responsible for BHT-Q formation. 36,37 Lipid micelles can stimulate the secretion of chylomicrons (i.e., apolipoprotein B (apoB) 48containing lipoproteins) by Caco-2 cells, and the cytochrome P450 isoenzyme can be found on the surfaces of the lipoproteins. 38,39 These may explain why metabolites were detected under the lipid state.…”

Identifying xenobiotic metabolites with in silico prediction tools and LCMS suspect screening analysis

“…Of the 33 parent compounds investigated in this study, no reported metabolites were included for 2-nitrotoluene, 3,5-dinitroaniline, butylated hydroxytoluene, or lindane. While there are studies that identify metabolites for lindane ( Fitzloff et al, 1982 ), 2-nitrotoluene ( DeBethizy and Rickert, 1984 ) and butylated hydroxytoluene ( Conning and Phillips, 1986 ), these articles were not identified by the authors prior to generation of the MS 2 spectra suspect screening library.…”

Metabolism of a Bioorthogonal PET Tracer Candidate [19F/18F]SiFA-Tetrazine in Mouse Liver Microsomes: Biotransformation Pathways and Defluorination Investigated by UHPLC-HRMS

“…The metabolism of 2,6-di- tert -butyl- p -cresol (BHT) demonstrated species-specific oxidation, with the aromatic ring bound methyl group being hydroxylated in rat, rabbit, and monkey, and tert -butyl groups in human. 50 In all the aforementioned compounds, the sp 3 -carbon was oxidized in the presence of an aromatic ring, which was left intact. This supports the hypothesis that SiFA–Tz is likely oxidized from the tert -butyl groups adjacent to the silicon atom.…”

“…Previously reported findings on the metabolism of Finasteride and Docetaxel, both compounds containing a tert -butyl group and or aromatic ring, demonstrate that the tert -butyl undergoes oxidation at one sp 3 -carbon rather than an aromatic ring. The metabolism of 2,6-di- tert -butyl- p -cresol (BHT) demonstrated species-specific oxidation, with the aromatic ring bound methyl group being hydroxylated in rat, rabbit, and monkey, and tert -butyl groups in human . In all the aforementioned compounds, the sp 3 -carbon was oxidized in the presence of an aromatic ring, which was left intact.…”

Effects of Food Constituents on Absorption and Bioaccessibility of Dietary Synthetic Phenolic Antioxidant by Caco-2 Cells

“…After a 5 h exposure, BHT-Q in the cell compartment was 7.56 ± 0.30% of the initial BHT dose and BHT-Q in apical and basolateral compartments was only 0.07 ± 0.003 and 0.04 ± 0.01%, respectively (Figure ). Oxidative metabolism (phase I reactions), mediated by a cytochrome P450 monooxygenase, is the major route for BHT transformation, and BHT activation has been ascribed to the activity of the CYP2B enzyme, which may be responsible for BHT-Q formation. , Lipid micelles can stimulate the secretion of chylomicrons (i.e., apolipoprotein B (apoB) 48-containing lipoproteins) by Caco-2 cells, and the cytochrome P450 isoenzyme can be found on the surfaces of the lipoproteins. , These may explain why metabolites were detected under the lipid state. In contrast to BHT-Q and BHT-quinol, the metabolites of the oxidation of the alkyl substituents pathway of BHT, i.e., BHT-OH, BHT-CHO, and BHT-COOH, were not detected in any of the nutrient conditions.…”

“…Oxidative metabolism (phase I reactions), mediated by a cytochrome P450 monooxygenase, is the major route for BHT transformation, and BHT activation has been ascribed to the activity of the CYP2B enzyme, which may be responsible for BHT-Q formation. 36,37 Lipid micelles can stimulate the secretion of chylomicrons (i.e., apolipoprotein B (apoB) 48containing lipoproteins) by Caco-2 cells, and the cytochrome P450 isoenzyme can be found on the surfaces of the lipoproteins. 38,39 These may explain why metabolites were detected under the lipid state.…”