1,2-Diacetylbenzene, the neurotoxic metabolite of a chromogenic aromatic solvent, induces proximal axonopathy

Min Sun Kim, Mohammad I. Sabri, Victor H. Miller, Robert J. Kayton, David A. Dixon, Peter Spencer

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Several widely used aromatic hydrocarbon solvents reportedly induce blue-green discoloration of tissues and urine in animals and humans. The chomophore has been proposed to result from a ninhydrin-like reaction with amino groups in proteins. The present study examines the neurotoxic property of 1,2-diacetylbenzene (1,2-DAB), the active metabolite of the chromogenic and neurotoxic aromatic solvent 1,2-diethylbenzene. Rats treated with 1,2-DAB, but not with the nonchromogenic isomer 1,3-DAB or with ninhydrin developed blue discoloration of internal organs, including the brain and spinal cord. Only 1,2-DAB induced limb weakness associated with nerve fiber changes, which were most prominent in spinal cord and spinal roots. Changes began with the formation of proximal, neurofilament-filled axonal swellings of the type seen after treatment with 3,4-dimethyl-2,5-hexanedione, a potent derivative of the active metabolite of the neurotoxic aliphatic hydrocarbon solvents n-hexane and methyl n-butyl ketone. These compounds are metabolized to a γ-diketone that forms pyrroles with target proteins, such as neurofilament proteins. A comparable mechanism is considered for 1,2-DAB, an aromatic γ-diketone.

Original languageEnglish (US)
Pages (from-to)121-131
Number of pages11
JournalToxicology and Applied Pharmacology
Volume177
Issue number2
DOIs
StatePublished - Dec 1 2001

Fingerprint

Chromogenics
Metabolites
Ninhydrin
Discoloration
Spinal Cord
Methyl n-Butyl Ketone
Neurofilament Proteins
Aromatic Hydrocarbons
Pyrroles
Intermediate Filaments
Spinal Nerve Roots
Hydrocarbons
Nerve Fibers
Isomers
Swelling
Rats
Brain
Animals
Proteins
Extremities

Keywords

  • Aromatic solvent
  • Axonopathy
  • Chromophore
  • Diacetylbenzene
  • Diethylbenzene
  • Green urine
  • Neuropathy
  • Ninhydrin
  • Tetralin

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

1,2-Diacetylbenzene, the neurotoxic metabolite of a chromogenic aromatic solvent, induces proximal axonopathy. / Kim, Min Sun; Sabri, Mohammad I.; Miller, Victor H.; Kayton, Robert J.; Dixon, David A.; Spencer, Peter.

In: Toxicology and Applied Pharmacology, Vol. 177, No. 2, 01.12.2001, p. 121-131.

Research output: Contribution to journalArticle

Kim, Min Sun ; Sabri, Mohammad I. ; Miller, Victor H. ; Kayton, Robert J. ; Dixon, David A. ; Spencer, Peter. / 1,2-Diacetylbenzene, the neurotoxic metabolite of a chromogenic aromatic solvent, induces proximal axonopathy. In: Toxicology and Applied Pharmacology. 2001 ; Vol. 177, No. 2. pp. 121-131.
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