Nonoxidative metabolism of 2-butoxyethanol via fatty acid conjugation in Fischer 344 rats

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Abstract

Nonoxidative metabolism of ethylene glycol monobutyl ether (2-butoxyethanol or BE) via fatty acid conjugation was studied in the liver of Fischer 344 male rats following a single oral administration of 500 mg/kg body weight [ethyl-1,2-14C]BE (70 μCi/kg). Animals were killed 2 h after the treatment, hepatic lipids extracted, and the neutral lipids were separated using solid-phase extraction. The neutral lipid fraction was subjected to preparative thin layer chromatography, and the esters corresponding to the relative flow of authentic fatty acid 2-butoxyethyl esters were recovered and analyzed by reversed-phase high-performance liquid chromatography (HPLC) using methanol-water (37:3, v/v) as solvent. Approximately 85% of the 14C label present in the ester fraction was coeluted at retention times corresponding to the different fatty acid 2-butoxyethyl ester standards. The radioactive fractions were analyzed by electron impact mass spectrometry. Molecular ion peaks and fragmentation patterns similar to that of 16:0, 18:0, 18:1, 18:2, and 20:4 fatty acid 2-butoxyethyl ester standards were detected in the corresponding radioactive HPLC fractions. Fatty acid ethyl ester synthase (FAEE5), purified from the rat liver microsomal fraction, was also found to catalyze the formation of 18:1 fatty acid 2-butoxyethyl ester. These studies demonstrate that BE is metabolized nonoxidatively via conjugation with long-chain fatty acids, and the formation of these esters appears to be catalyzed by the enzyme(s) involved in fatty acid conjugation of xenobiotic alcohols. However, the biological significance of BE conjugation with fatty acids remains to be investigated.

Original languageEnglish (US)
Pages (from-to)463-479
Number of pages17
JournalJournal of Toxicology and Environmental Health
Volume49
Issue number5
StatePublished - 1996

Fingerprint

Inbred F344 Rats
Fatty acids
Metabolism
Rats
ester
Fatty Acids
fatty acid
metabolism
Esters
Lipids
High performance liquid chromatography
lipid
Liver
liquid chromatography
High Pressure Liquid Chromatography
Thin layer chromatography
Ethylene Glycol
n-butoxyethanol
Solid Phase Extraction
Xenobiotics

ASJC Scopus subject areas

  • Toxicology
  • Pollution
  • Environmental Science(all)
  • Environmental Chemistry
  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health

Cite this

@article{3eac4c7e8eac4912ad8bdb2abb87272a,
title = "Nonoxidative metabolism of 2-butoxyethanol via fatty acid conjugation in Fischer 344 rats",
abstract = "Nonoxidative metabolism of ethylene glycol monobutyl ether (2-butoxyethanol or BE) via fatty acid conjugation was studied in the liver of Fischer 344 male rats following a single oral administration of 500 mg/kg body weight [ethyl-1,2-14C]BE (70 μCi/kg). Animals were killed 2 h after the treatment, hepatic lipids extracted, and the neutral lipids were separated using solid-phase extraction. The neutral lipid fraction was subjected to preparative thin layer chromatography, and the esters corresponding to the relative flow of authentic fatty acid 2-butoxyethyl esters were recovered and analyzed by reversed-phase high-performance liquid chromatography (HPLC) using methanol-water (37:3, v/v) as solvent. Approximately 85{\%} of the 14C label present in the ester fraction was coeluted at retention times corresponding to the different fatty acid 2-butoxyethyl ester standards. The radioactive fractions were analyzed by electron impact mass spectrometry. Molecular ion peaks and fragmentation patterns similar to that of 16:0, 18:0, 18:1, 18:2, and 20:4 fatty acid 2-butoxyethyl ester standards were detected in the corresponding radioactive HPLC fractions. Fatty acid ethyl ester synthase (FAEE5), purified from the rat liver microsomal fraction, was also found to catalyze the formation of 18:1 fatty acid 2-butoxyethyl ester. These studies demonstrate that BE is metabolized nonoxidatively via conjugation with long-chain fatty acids, and the formation of these esters appears to be catalyzed by the enzyme(s) involved in fatty acid conjugation of xenobiotic alcohols. However, the biological significance of BE conjugation with fatty acids remains to be investigated.",
author = "Bhupendra Kaphalia and Ghanayem, {B. I.} and Ghulam Ansari",
year = "1996",
language = "English (US)",
volume = "49",
pages = "463--479",
journal = "Journal of Toxicology and Environmental Health - Part A: Current Issues",
issn = "1528-7394",
publisher = "Taylor and Francis Ltd.",
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TY - JOUR

T1 - Nonoxidative metabolism of 2-butoxyethanol via fatty acid conjugation in Fischer 344 rats

AU - Kaphalia, Bhupendra

AU - Ghanayem, B. I.

AU - Ansari, Ghulam

PY - 1996

Y1 - 1996

N2 - Nonoxidative metabolism of ethylene glycol monobutyl ether (2-butoxyethanol or BE) via fatty acid conjugation was studied in the liver of Fischer 344 male rats following a single oral administration of 500 mg/kg body weight [ethyl-1,2-14C]BE (70 μCi/kg). Animals were killed 2 h after the treatment, hepatic lipids extracted, and the neutral lipids were separated using solid-phase extraction. The neutral lipid fraction was subjected to preparative thin layer chromatography, and the esters corresponding to the relative flow of authentic fatty acid 2-butoxyethyl esters were recovered and analyzed by reversed-phase high-performance liquid chromatography (HPLC) using methanol-water (37:3, v/v) as solvent. Approximately 85% of the 14C label present in the ester fraction was coeluted at retention times corresponding to the different fatty acid 2-butoxyethyl ester standards. The radioactive fractions were analyzed by electron impact mass spectrometry. Molecular ion peaks and fragmentation patterns similar to that of 16:0, 18:0, 18:1, 18:2, and 20:4 fatty acid 2-butoxyethyl ester standards were detected in the corresponding radioactive HPLC fractions. Fatty acid ethyl ester synthase (FAEE5), purified from the rat liver microsomal fraction, was also found to catalyze the formation of 18:1 fatty acid 2-butoxyethyl ester. These studies demonstrate that BE is metabolized nonoxidatively via conjugation with long-chain fatty acids, and the formation of these esters appears to be catalyzed by the enzyme(s) involved in fatty acid conjugation of xenobiotic alcohols. However, the biological significance of BE conjugation with fatty acids remains to be investigated.

AB - Nonoxidative metabolism of ethylene glycol monobutyl ether (2-butoxyethanol or BE) via fatty acid conjugation was studied in the liver of Fischer 344 male rats following a single oral administration of 500 mg/kg body weight [ethyl-1,2-14C]BE (70 μCi/kg). Animals were killed 2 h after the treatment, hepatic lipids extracted, and the neutral lipids were separated using solid-phase extraction. The neutral lipid fraction was subjected to preparative thin layer chromatography, and the esters corresponding to the relative flow of authentic fatty acid 2-butoxyethyl esters were recovered and analyzed by reversed-phase high-performance liquid chromatography (HPLC) using methanol-water (37:3, v/v) as solvent. Approximately 85% of the 14C label present in the ester fraction was coeluted at retention times corresponding to the different fatty acid 2-butoxyethyl ester standards. The radioactive fractions were analyzed by electron impact mass spectrometry. Molecular ion peaks and fragmentation patterns similar to that of 16:0, 18:0, 18:1, 18:2, and 20:4 fatty acid 2-butoxyethyl ester standards were detected in the corresponding radioactive HPLC fractions. Fatty acid ethyl ester synthase (FAEE5), purified from the rat liver microsomal fraction, was also found to catalyze the formation of 18:1 fatty acid 2-butoxyethyl ester. These studies demonstrate that BE is metabolized nonoxidatively via conjugation with long-chain fatty acids, and the formation of these esters appears to be catalyzed by the enzyme(s) involved in fatty acid conjugation of xenobiotic alcohols. However, the biological significance of BE conjugation with fatty acids remains to be investigated.

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