Metabolism and disposition of 1-bromopropane in rats and mice following inhalation or intravenous administration

Garner, C. Edwin; Sumner, Susan; Davis, Jefferson; Burgess, Jason P.; Yueh, Yun Lan; Demeter, Jennifer; Zhan, Qiao; Valentine, J L; Jeffcoat, A; Burka, Leo T.; Mathews, James

doi:10.1016/j.taap.2006.01.010

Cited by 42 publications

(49 citation statements)

References 34 publications

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“…The animals then were transferred to standard metabolic cages, and urine samples were collected for 24 h. The levels of deuterated chlorotyrosine, tyrosine, chloro-HPA, and HPA were measured in the collected urine samples as described above. To determine whether the observed dechlorination of chlorotyrosine was dependent on a cytochrome P450, one group of rats (n ϭ 3) were pre-treated with 1-aminobenzotriazole (50 mg/kg) to block cytochrome P450 activity at 24 and 4 h before the intraperitoneal injection of 0.50 mol [D 4 ]chlorotyrosine (20). Urine was collected over 24 h and analyzed as above.…”

Section: Measurement Of Chlorotyrosine and Tyrosine By Gc/ms-mentioning

confidence: 99%

The Metabolism and Dechlorination of Chlorotyrosine in Vivo

Mani

Ippolito

Moreno

et al. 2007

Journal of Biological Chemistry

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During inflammation, neutrophil-and monocyte-derived myeloperoxidase catalyzes the formation of hypochlorous acid, which can chlorinate tyrosine residues in proteins to form chlorotyrosine. However, little is known of the metabolism and disposition of chlorotyrosine in vivo. Following infusion of deuteriumlabeled [D 4 ]chlorotyrosine into Sprague-Dawley rats, the major urinary metabolites were identified by mass spectrometry. 3-Chloro-4-hydroxyphenylacetic acid was identified as the major chlorinated metabolite of chlorotyrosine and accounted for 3.6 ؎ 0.3% of infused [D 4 ]chlorotyrosine. The striking observation was that ϳ40% (39 ؎ 1%) of infused [D 4 ]chlorotyrosine was dechlorinated and excreted in the urine as deuterated 4-hydroxyphenylacetic acid, a major metabolite of tyrosine. 1.1 ؎ 0.1% of infused [D 4 ]chlorotyrosine was excreted as [D 4 ]tyrosine.To determine whether protein-bound chlorotyrosine could undergo dechlorination, chlorinated albumin was incubated with liver homogenate from mutant rats, which did not synthesize albumin. There was ϳ20% decrease in the chlorotyrosine content over 1 h. This study is the first to describe the dechlorination of chlorotyrosine as the major metabolic pathway to eliminate this modified amino acid in vivo. Myeloperoxidase (MPO)3 is a phagocytic enzyme secreted during inflammation, which undergoes transcytosis into vascular endothelium where it can lead to vascular dysfunction (1, 2). Myeloperoxidase catalyzes the formation of hypochlorous acid, a potent chlorinating reagent, from hydrogen peroxide and chloride anion. In turn, hypochlorous acid can react with nitrite to form nitryl chloride (3, 4). Hypochlorous acid and nitryl chloride can react with tyrosyl residues in proteins to form chlorotyrosine and nitrotyrosine, respectively (3, 4). Thus, the measurement of chlorotyrosine has been extensively used to assess the formation of MPO-derived hypochlorous acid in vivo (5, 6). Likewise measurement of nitrotyrosine has been used as a footprint for the formation of peroxynitrite or nitryl chloride in vivo (1, 7-9). However, one of the major disadvantages of measuring chlorotyrosine or nitrotyrosine is that modified proteins may undergo rapid catabolism (10), and the resulting free chlorotyrosine or nitrotyrosine are taken up by cells, metabolized, and excreted. Thus, it is well established that nitrotyrosine is metabolized to 3-nitro-4-hydroxy-phenylacetic acid (nitro-HPA), which is the major urinary metabolite (11, 12), and urinary levels increase during endotoxemia (12).Tyrosine is iodinated by iodine in a reaction catalyzed by thyroid peroxidase to form iodotyrosine, a key intermediate in thyroid hormone synthesis. It is well recognized that pathways exist for the dehalogenation of iodotyrosine to form tyrosine in vivo (13), and historically this pathway has been assumed to exist for the conservation of iodine. Iodotyrosine dehalogenase, which catalyzes the deiodination of iodotyrosine to tyrosine and iodide, was characterized over 50 years ago (13). This enzyme ...

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Section: Measurement Of Chlorotyrosine and Tyrosine By Gc/ms-mentioning

confidence: 99%

The Metabolism and Dechlorination of Chlorotyrosine in Vivo

Mani

Ippolito

Moreno

et al. 2007

Journal of Biological Chemistry

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“…Garner et al (2006) observed that 1-BP metabolic pathways differed between species; in rats, but not mice, the predominant pathway was shown to vary with dose. The authors reported that oxidation via cytochrome P-450 was the predominant pathway because when P-450 oxidation was inhibited (or saturated at high doses), AcPrCys became predominant from S-glutathione conjugation.…”

Section: Discussionmentioning

confidence: 97%

“…1 that includes exhalation of unaltered 1-BP, debromination releasing free Br (-) ion, oxidation by CYP2E1, and S-conjugation with glutathione (Barnsley et al 1966;Walsh 1979, 1980;Garner et al 2006). An intermediate metabolite, S-n-propyl-glutathione, is cleaved to S-n-propyl-L-cysteine, which is metabolized producing several mercapturic acid conjugates excreted in urine.…”

Section: Introductionmentioning

confidence: 99%

Bromide and N-acetyl-S-(n-propyl)-l-cysteine in urine from workers exposed to 1-bromopropane solvents from vapor degreasing or adhesive manufacturing

Hanley

Petersen

Cheever

et al. 2010

Int Arch Occup Environ Health

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“…Nach intravenöser Injektion von 3b is 100 mg radioaktiv markiertem 14 C-1-Brompropan /kg KG exhalierten Ratten und Mäuse den Hauptteil der Dosis als flüchtige organische Ve rbindungen (40-70%) (Garner et al 2006). Bei einem Großteil hiervon dürfte es sich um nicht-metabolisiertes 1-Brompropan handeln, wie von Jones und Walsh 1979 gezeigt.…”

Section: Metabolismusunclassified

“…Der Anteil der im Urin nachgewiesenen Radioaktivität lag für Ratten bei 13 bis 17% und für Mäuse bei 14 bis 23%. Der Anteil an Radioaktivität in den Faeces betrug bei Ratten 2,1% und bei Mäusen 3,7% und der Anteil der im Körper verbliebenen Aktivität 6,1% bei Ratten und 3,9% bei Mäusen (Garner et al 2006). Eine genauere Untersuchung derM etabolisierung von1 -Brompropane rbrachte,d ass 1-Brompropan beiRattenund Mäusen nach 6-stündigeri nhalativer Exposition (800 ml/ m 3 )odernachintravenöserInjektion(20-100mg/kg KG)entwederdirekt mitGSH konjugiertoderals HauptmetabolisierungswegüberCytochrom-P450(CYP)-abhängige Oxidation (u.a.C YP2E1) zu 1-Brom-2-hydroxypropan (1-Brom-2-propanol)o xidiertw ird.…”

Section: Metabolismusunclassified

1‐Brompropan [MAK Value Documentation in German language, 2011]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 50. Lieferung, Ausgabe 2011 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Wirkungsmechanismus Toxikokinetik und Metabolismus Aufnahme, Verteilung, Ausscheidung Metabolismus Erfahrungen beim Menschen Einmalige Exposition Wiederholte Exposition Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Tierexperimentelle Befunde und In‐vitro‐Untersuchungen Akute Toxizität Subakute, subchronische und chronische Toxizität Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Bewertung

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Metabolism and disposition of 1-bromopropane in rats and mice following inhalation or intravenous administration

Cited by 42 publications

References 34 publications

The Metabolism and Dechlorination of Chlorotyrosine in Vivo

The Metabolism and Dechlorination of Chlorotyrosine in Vivo

Bromide and N-acetyl-S-(n-propyl)-l-cysteine in urine from workers exposed to 1-bromopropane solvents from vapor degreasing or adhesive manufacturing

1‐Brompropan [MAK Value Documentation in German language, 2011]

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