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Forensic Toxicology

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01.01.2019 | Original Article

Metabolism of triacetone triperoxide (TATP) by canine cytochrome P450 2B11

verfasst von: Kevin Colizza, Michelle Gonsalves, Lindsay McLennan, James L. Smith, Jimmie C. Oxley

Erschienen in: Forensic Toxicology | Ausgabe 1/2019

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Abstract

Purpose

This work is performed to determine if there is a potential for the accumulation and potential toxicity of triacetone triperoxide (TATP) in canines. Additional utility of this information may suggest human toxicity and possibly detection of biomarkers, metabolites or intact molecule of those using this material for nefarious reasons.

Methods

Liquid chromatography/mass spectrometry of dog liver microsome (DLM) incubation samples of TATP was used to measure substrate depletion. Trapping of electrophilic products was performed using glutathione (GSH) and semicarbazide. Comparisons were made to free hydroperoxides found in methyl ethyl ketone peroxides (MEKP).

Results

The non-specific K_m value of 2.2 μM and a V_max of 1.1 nmol/min/mg of protein were determined. Canine recombinant cytochrome P450 (rCYP) 2B11 with human cytochrome b5 was found to catalyze the NADPH-dependent metabolism of TATP into its only phase I metabolite, hydroxy-TATP (TATP-OH). No secondary metabolite(s) or degraded products were detected or trapped from microsomal incubations. MEKP subjected to similar conditions was found to undergo significant metabolism, semicarbazide trapping and rapid oxidation of GSH to GSSG. The synthesized TATP-OH metabolite incubated in DLM progressed three times faster than TATP metabolism with no secondary metabolites found or trapped.

Conclusions

TATP does not react as MEKP suggesting that TATP does not ring-open to form hydroperoxides. TATP and TATP-OH compete for the same enzyme, with TATP dominating this competition. Failure to detect additional metabolite(s) suggests they may be too small to detect by our system or bound covalently to a protein or polymer in the incubation reaction.

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Titel: Metabolism of triacetone triperoxide (TATP) by canine cytochrome P450 2B11
verfasst von: Kevin Colizza
Michelle Gonsalves
Lindsay McLennan
James L. Smith
Jimmie C. Oxley
Publikationsdatum: 01.01.2019
Verlag: Springer Japan
Erschienen in: Forensic Toxicology / Ausgabe 1/2019
Print ISSN: 1860-8965
Elektronische ISSN: 1860-8973
DOI: https://doi.org/10.1007/s11419-018-0450-9

Springer Medizin

Metabolism of triacetone triperoxide (TATP) by canine cytochrome P450 2B11

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Rechtsmedizin

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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