Metabolomic profiling of the effects of allopurinol on Drosophila melanogaster

Mohammed Al Bratty, Yahya Hobani, Julian A. T. Dow, David G. Watson, David Watson

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16 Citations (Scopus)

Abstract

Metabolomic profiling using hydrophilic interaction chromatography in combination with Fourier transform mass spectrometry was used to study the effects of the xanthine oxidase inhibitor allopurinol on wild type Drosophila melanogaster. Allopurinol treatment phenocopied the rosy mutation causing an elevation in the levels of xanthine and hypoxanthine and a fall in the levels of uric acid and allantoin. However, in addition there were some unexpected metabolic changes after treatment. Ascorbic acid levels were undetectable, glutathione levels fell and glutathione disulphide levels rose, methionine S-oxide levels rose and riboflavin levels fell. The origin of this oxidative stress was not immediately apparent; however, there was a strong suggestion that it might be related to a fall in NADPH levels linked to a reduction in glucose-6-phosphate dehydrogenase activity, resulting in reduced levels of some metabolites in the pentose phosphate pathway. In addition to producing oxidative stress there were marked effects on tryptophan metabolism with most of the metabolites in the kynurenine pathway being lowered by allopurinol treatment. The effects on the kynurenine pathway could be related to the established use of allopurinol in treating schizophrenia.

Original languageEnglish
Pages (from-to)542-548
Number of pages7
JournalMetabolomics
Volume7
Issue number4
DOIs
Publication statusPublished - Dec 2011

Keywords

  • drosophila
  • metabolomics
  • rosy
  • Fourier transform mass spectrometry
  • allopurinol
  • oxidative stress
  • kynurenine pathway
  • uric acid
  • stress
  • double blind
  • urate
  • schizophrenia
  • antioxidant
  • stroke

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  • Cite this

    Al Bratty, M., Hobani, Y., Dow, J. A. T., Watson, D. G., & Watson, D. (2011). Metabolomic profiling of the effects of allopurinol on Drosophila melanogaster. Metabolomics, 7(4), 542-548. https://doi.org/10.1007/s11306-011-0275-6