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

Colizza, Kevin; Gonsalves, Michelle; McLennan, Lindsay; Smith, James L.; Oxley, Jimmie C.

doi:10.1007/s11419-018-0450-9

Cited by 7 publications

(14 citation statements)

References 40 publications

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“…As previously observed, TATP incubations in different species (dogs and rats) yielded the same metabolite, TATP-OH ( Fig. S5) [15]. Other suspected metabolites, including the dihydroxy-species and additional oxidation of the TATP-OH to the aldehyde and carboxylic acid were not observed.…”

Section: Metabolite Identificationsupporting

confidence: 82%

“…Biotransformation studies indicate that artemisinin is primarily metabolized by CYP2B6 to deoxyartemisinin, deoxydihydroartemisinin, dihydroartemisinin and ‘crystal-7’ [ 13 , 14 ]. Similarly, we have previously shown that TATP is metabolized in vitro by canine CYP2B11, another CYP2B subfamily enzyme [ 15 ]. Artemisinin is further metabolized by glucuronidation, particularly by UGT1A9 and UGT2B7, to dihydroartemisinin-glucuronide, the principal metabolite found in urine, suggesting endoperoxides, like TATP, may be glucuronidated and excreted in urine [ 16 ].…”

Section: Introductionmentioning

confidence: 91%

“…Furthermore, bomb-sniffing dogs and their handlers are purposely exposed to these vapors for the sake of training. Our previous study revealed TATP metabolism in dog liver microsomes (DLM) [ 15 ]. Now we evaluate its in vitro biotransformation in human liver microsomes (HLM) and recombinant enzymes, identifying phase I and phase II metabolites, estimating enzyme kinetics and also detecting urinary in vivo metabolites excreted from scientists exposed to TATP in their work environment.…”

Section: Introductionmentioning

confidence: 99%

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In vitro and in vivo studies of triacetone triperoxide (TATP) metabolism in humans

et al. 2020

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Purpose Triacetone triperoxide (TATP) is a volatile but powerful explosive that appeals to terrorists due to its ease of synthesis from household items. For this reason, bomb squad, canine (K9) units, and scientists must work with this material to mitigate this threat. However, no information on the metabolism of TATP is available. Methods In vitro experiments using human liver microsomes and recombinant enzymes were performed on TATP and TATP-OH for metabolite identification and enzyme phenotyping. Enzyme kinetics for TATP hydroxylation were also investigated. Urine from laboratory personnel collected before and after working with TATP was analyzed for TATP and its metabolites. Results While experiments with flavin monooxygenases were inconclusive, those with recombinant cytochrome P450s (CYPs) strongly suggested that CYP2B6 was the principle enzyme responsible for TATP hydroxylation. TATP-O-glucuronide was also identified and incubations with recombinant uridine diphosphoglucuronosyltransferases (UGTs) indicated that UGT2B7 catalyzes this reaction. Michaelis-Menten kinetics were determined for TATP hydroxylation, with K m = 1.4 µM and V max = 8.7 nmol/min/nmol CYP2B6. TATP-O-glucuronide was present in the urine of all three volunteers after being exposed to TATP vapors showing good in vivo correlation to in vitro data. TATP and TATP-OH were not observed. Conclusions Since scientists working to characterize and detect TATP to prevent terrorist attacks are constantly exposed to this volatile compound, attention should be paid to its metabolism. This paper is the first to elucidate some exposure, metabolism and excretion of TATP in humans and to identify a marker of TATP exposure, TATP-O-glucuronide in urine.

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Section: Metabolite Identificationsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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In vitro and in vivo studies of triacetone triperoxide (TATP) metabolism in humans

et al. 2020

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“…Oxley et al, in one of their works tried to determine whether there is a potential for the accumulation and toxicity of triacetone triperoxide (TATP) in canines [131]. Additionally this information may suggest human toxicity of TATP and could give some clues about possible detection of biomarkers, metabolites or intact molecule of those using this material for nefarious reasons.…”

Section: Hazardous Effects and Metabolismmentioning

confidence: 99%

“…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 the system employed or bound covalently to a protein or polymer in the incubation reaction [131].…”

Section: Hazardous Effects and Metabolismmentioning

confidence: 99%

Peroxide Based Organic Explosives

Türker

2021

EJCS

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In recent years progressively increasing terrorist activities, which use homemade explosives; such as acetone peroxide and other cyclic organic peroxides have led to worldwide awareness by security and defense agencies. Then the development of methodologies for the detection of cyclic organic peroxides have become an urgent need. Until quite recently, most of the current technology in use for trace detection of explosives had been unable to detect these energetic compounds. Differences in physical properties between cyclic organic peroxides is the main barrier for the development of a general method for analysis and detection of the peroxide explosives. In this short review, the most relevant contributions related to preparation, characterization and detection of the most important cyclic organic peroxides have been presented. It also includes few recent investigations about the toxicity and metabolism of some peroxide explosives.

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